FORMATO PER IL CURRICULUM VITAE - polime.it · 2020. 5. 25. · 2014. -docente di microbiologia...

FORMATO

EUROPEO

PER IL

CURRICULUM

VITAE

INFORMAZIONIPERSONALI

Nome

MANCUSO GIUSEPPE

Telefono

+39 (090) 221 3317

Fax

3312

Curriculum Vitae - MANCUSO Giuseppe https://www.polime.it/curriculum/view_cv.php?id_curriculum=35

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E-mail

[email protected]

Nazionalità

ITALIANA

Data di Nascita

14/04/1960

ESPERIENZALAVORATIVA

Date (da - a)

08/03/1999 -

Nome e indirizzo deldatore di lavoro

UNIVERSITÀ DI MESSINA, PIAZZA PUGLIATTI 1, 98100MESSINA

Tipo di azienda o settore

ISTRUZIONE

Tipo di impiego

PROFESSORE ASSOCIATO

Principali mansioni e


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responsabilità

-NOMINATO RICERCATORE UNIVERSITARIO PER ILRAGGRUPPAMENTO SCIENTIFICO-DISCIPLINAREMED/04 IN DATA 08/03/1999 PRESSO IL DIPARTIMENTODI PATOLOGIA E MICROBIOLOGIA SPERIMENTALEDELLA FACOLTÀ DI MEDICINA E CHIRURGIADELL’UNIVERSITÀ DEGLI STUDI DI MESSINA. DAL01/10/2012 AFFERISCE AL DIPARTIMENTO DI SCIENZEPEDIATRICHE, GINECOLOGICHE, MICROBIOLOGICHEE BIOMEDICHE DELL’UNIVERSITÀ DEGLI STUDI DIMESSINA. -DIRETTORE DELLO STABILIMENTOUTILIZZATORE ED ALLEVATORE DEL DIPARTIMENTODI PATOLOGIA E MICROBIOLOGIA SPERIMENTALE(2006-2010), DEL DIPARTIMENTO DI SCIENZEPEDIATRICHE, GINECOLOGICHE, MICROBIOLOGICHEE BIOMEDICHE (2010-2015) E DEL DIPARTIMENTO DIPATOLOGIA UMANA DELL'ADULTO E DELL'ETÀEVOLUTIVA "G. BARRESI) (2015 A TUTT'OGGI). -NEL2014 HA CONSEGUITO L'ABILITAZIONE SCIENTIFICANAZIONALE PER PROFESSORE ASSOCIATO DIMICROBIOLOGIA GENERALE E MICROBIOLOGIACLINICA (SSD MED07) E DI PATOLOGIA GENERALE(SSD MED04). -NOMINATO PROFESSORE ASSOCIATOPER IL RAGGRUPPAMENTO SCIENTIFICO-DISCIPLINARE MED/07 IN DATA 01/11/2014 PRESSO ILDIPARTIMENTO DI PATOLOGIA E MICROBIOLOGIASPERIMENTALE DELL’UNIVERSITÀ DEGLI STUDI DIMESSINA. -VICEPRESIDENTE DELL'ORGANISMOPREPOSTO AL BENESSERE ANIMALE (OPBA)DELL'UNIVERSITÀ DEGLI STUDI DI MESSINA (2014 ATUTT'OGGI). -DAL 01/10/2015 AFFERISCE ALDIPARTIMENTO DI PATOLOGIA UMANA DELL'ADULTO EDELL'ETÀ EVOLUTIVA "G. BARRESI" DELL'UNIVERSITÀDEGLI STUDI DI MESSINA. -DIRIGENTE MEDICO DI I°LIVELLO PRESSO L’UNITÀ OPERATIVA COMPLESSA DIMICOLOGIA E MICOBATTERIOLOGIA DELL’AZIENDAOSPEDALIERA UNIVERSITARIA “G. MARTINO” DIMESSINA DAL 1999 AL 2009. -DIRIGENTE MEDICO DI I°LIVELLO PRESSO LA SEZIONE DI MICOLOGIA EMICOBATTERIOLOGIA ED IL LABORATORIOCENTRALIZZATO DELL’UNITÀ OPERATIVA COMPLESSADI PATOLOGIA CLINICA DELL’AZIENDA OSPEDALIERAUNIVERSITARIA “G. MARTINO” DI MESSINA DAL 2010AL 2017. -DIRIGENTE MEDICO DI I° LIVELLO PRESSOL’UNITÀ OPERATIVA COMPLESSA DI MICROBIOLOGIACLINICA DELL’AZIENDA OSPEDALIERAUNIVERSITARIA “G. MARTINO” DI MESSINA DAL 1°APRILE 2017 A TUTT'OGGI. -DIRETTORE VICARIO


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DELL'UNITÀ OPERATIVA COMPLESSA DIMICROBIOLOGIA CLINICA DELL'AZIENDAOSPEDALIERA UNIVERSITARIA "G. MARTINO" DIMESSINA DAL 1° GENNAIO 2018 A TUTT'OGGI. -DAL14/04/2011 TITOLARE DI UN INCARICO DI ALTAPROFESSIONALITÀ CONFERITOGLI DAL DIRETTOREGENERALE DELL’AZIENDA OSPEDALIERAUNIVERSITARIA “G. MARTINO” DI MESSINA. -DOCENTEDI MICROBIOLOGIA NEL CORSO DI LAUREA DIFISIOTERAPISTA DELLA FACOLTÀ DI MEDICINA ECHIRURGIA DELL’UNIVERSITÀ DEGLI STUDI DIMESSINA PER GLI AA 2000-2001 E 2001-2002.-DOCENTE DI VIROLOGIA CLINICA APPLICATA ALLAMICROBIOLOGIA NELLA SCUOLA DISPECIALIZZAZIONE DI MICROBIOLOGIA E VIROLOGIADELLA FACOLTÀ DI MEDICINA E CHIRURGIADELL’UNIVERSITÀ DEGLI STUDI DI MESSINADALL’ANNO ACCADEMICO 1999-2000. -DOCENTE DIPATOLOGIA GENETICA NELLA SCUOLA DISPECIALIZZAZIONE DI PATOLOGIA CLINICA DELLAFACOLTÀ DI MEDICINA E CHIRURGIADELL’UNIVERSITÀ DEGLI STUDI DI MESSINA PERL’ANNO ACCADEMICO 2002-2003. -DOCENTE DIMICROBIOLOGIA GENERALE E MICROBIOLOGIACLINICA NEL CORSO DI LAUREA PER ORTOTTISTIASSISTENTI DI OFTALMOLOGIA DELLA FACOLTÀ DIMEDICINA E CHIRURGIA DELL’UNIVERSITÀ DEGLISTUDI DI MESSINA DALL’AA 2002-2003.-COORDINATORE CORSO INTEGRATO DI SCIENZEBIOLOGICHE I NEL CORSO DI LAUREA PERORTOTTISTI ASSISTENTI DI OFTALMOLOGIA DELLAFACOLTÀ DI MEDICINA E CHIRURGIADELL’UNIVERSITÀ DEGLI STUDI DI MESSINA DALL’AA2011 A TUTT'OGGI. -DOCENTE DI MICROBIOLOGIACLINICA NEL CORSO INTEGRATO DI MEDICINA DILABORATORIO NEL CDL DI MEDICINA E CHIRURGIANELL'AA 2014-2015. -DOCENTE DI MICROBIOLOGIAGENERALE E MICROBIOLOGIA CLINICA NEL CORSOINTEGRATO DI BASI BIOLOGICHE E MOLECOLARI DELCDL DI FISIOTERAPIA DALL'AA 2015-2016 ATUTT'OGGI. -DOCENTE DI MICROBIOLOGIAGENERALE E MICROBIOLOGIA CLINICA NEL CORSOINTEGRATO DI PROMOZIONE DELLA SALUTE E DELLASICUREZZA DEL CDL DI INFERMIERISTICA DALL'AA2015-2016 A TUTT'OGGI. -DOCENTE DIMICROBIOLOGIA GENERALE E MICROBIOLOGIACLINICA NEL CORSO INTEGRATO DI SCIENZEBIOLOGICHE DEL CDL DI TECNICHE DELLAPREVENZIONE NELL'AMBIENTE E NEI LUOGHI DI


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LAVORO DALL'AA 2015-2016 A TUTT'OGGI. -DOCENTEDI STATISTICA MEDICA NELLA SCUOLA DISPECIALIZZAZIONE DI MICROBIOLOGIA E VIROLOGIADELLA FACOLTÀ DI MEDICINA E CHIRURGIADELL’UNIVERSITÀ DEGLI STUDI DI MESSINADALL’ANNO ACCADEMICO 2010-2011 ALL'AA 2014.-DOCENTE DI PATOLOGIA GENERALE NELLA SCUOLADI SPECIALIZZAZIONE DI MICROBIOLOGIA EVIROLOGIA DELLA FACOLTÀ DI MEDICINA ECHIRURGIA DELL’UNIVERSITÀ DEGLI STUDI DIMESSINA DALL’ANNO ACCADEMICO 2010-2011 ALL'AA2014. -DOCENTE DI MICROBIOLOGIA GENERALE EMICROBIOLOGIA CLINICA NELLA SCUOLAAGGREGATA DI SPECIALIZZAZIONE DIMICROBIOLOGIA E VIROLOGIA AREA MEDICADELL’UNIVERSITÀ DEGLI STUDI DI CATANIADALL’ANNO ACCADEMICO 2014 A TUTT'OGGI.-COORDINATORE DELLA SCUOLA DISPECIALIZZAZIONE DI MICROBIOLOGIA E VIROLOGIAAREA SANITARIA NON MEDICA DELL'UNIVERSITÀDEGLI STUDI DI MESSINA DAL 31 MAGGIO 2018.-DOCENTE DI VIROLOGIA MOLECOLARE NELDOTTORATO DI RICERCA IN BIOTECNOLOGIEMICROBICHE E DELLA PROLIFERAZIONE CELLULAREDELL’UNIVERSITÀ DEGLI STUDI DI MESSINADALL’ANNO ACCADEMICO 2005-2006 ALL'AA2011-2012. NELL’AMBITO DEI VARI CICLI DELSUDDETTO DOTTORATO HA FATTO PARTE DIDIVERSE COMMISSIONI DI AMMISSIONE E/O DIDIPLOMA. -DOCENTE NEL DOTTORATO DI RICERCA INBIOTECNOLOGIE MEDICHE E CHIRURGICHEDELL'UNIVERSITÀ DEGLI STUDI DI MESSINA DALL'AA2013 A TUTT'OGGI.

Date (da - a)

08/03/1999 -


A.O.U. POLICLINICO UNIVERSITARIO DI MESSINA, VIACONSOLARE VALERIA 1, 98125 MESSINA



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SANITÀ

Tipo di impiego

DIRIGENTE MEDICO I° LIVELLO

Principali mansioni eresponsabilità

DIRIGENTE MEDICO CON FUNZIONE DI DIRETTOREVICARIO DELLA U.O.C. DI MICROBIOLOGIA CLINICA

Date (da - a)

14/12/1988 - 02/01/1990


MINISTERO DELLA DIFESA , EUR, ROMA


SANITÀ

Tipo di impiego

UFFICIALE MEDICO DI COMPLEMENTO

Principali mansioni eresponsabilità

DIRIGENTE SERVIZIO SANITARIO DISTRETTOMILITARE DI CASERTA

ISTRUZIONE EFORMAZIONE


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Date (da - a)

01/11/1993 - 31/10/1997

Nome e tipo di istituto diistruzione o formazione

FACOLTÀ MEDICINA E CHIRURGIA, UNIVERSITÀ DIMESSINA, MESSINA - ITALIA

Titolo di Studio

SPEC.NE IN MICROBIOLOGIA E VIROLOGIA

Qualifica conseguita

SPECIALISTA IN MICROBIOLOGIA E VIROLOGIA

Livello nellaclassificazione nazionale

50/50 CON LODE

Date (da - a)

01/11/1990 - 30/04/1994


UNIVERSITÀ DI CATANIA, ROMA - ITALIA

Titolo di Studio


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DOTTORATO DI RICERCA IN MICROBIOLOGIA DI BASEED APPLICATA


DOTTORE DI RICERCA IN DISCIPLINEMICROBIOLOGICHE


Date (da - a)

01/11/1985 - 31/10/1988


FACOLTÀ DI MEDICINA E CHIRURGIA, UNIVERSITÀ DIMESSINA, MESSINA - ITALIA

Titolo di Studio

SPEC.NE IN MICROBIOLOGIA


SPECIALISTA IN VIROLOGIA


50/50 CON LODE

Date (da - a)

01/09/1985 - 30/09/1985


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FACOLTÀ DI MEDICINA E CHIRURGIA, UNIVERSITÀ DIMESSINA, MESSINA - ITALIA

Titolo di Studio

ABILITAZIONE ALL'ESERCIZIO DELLA PROFESSIONEDI MEDICO CHIRURGO


ABILITATO ALL'ESERCIZIO DELLA PROFESSIONE DIMEDICO CHIRURGO


Date (da - a)

01/11/1978 - 19/07/1985


UNIVERSITÀ DI MESSINA, MESSINA - ITALIA

Titolo di Studio

LAUREA IN MEDICINA E CHIRURGIA


DOTTORE IN MEDICINA E CHIRURGIA

Livello nella


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classificazione nazionale

110/110 CON LODE

PUBBLICAZIONI

Titolo

PBSP, A CELL WALL-ANCHORED PROTEIN THAT BINDSPLASMINOGEN TO PROMOTE HEMATOGENOUSDISSEMINATION OF GROUP B STREPTOCOCCUS

Autori

BUSCETTA MARCO, FIRON ARNAUD, PIETROCOLAGIAMPIERO, BIONDO CARMELO, MANCUSO GIUSEPPE,MIDIRI ANGELINA, ROMEO LETIZIA, GALBO ROBERTA,VENZA MARIO, VENZA ISABELLA, KAMINSKI PIERRE-ALEXANDRE, GOMINET MYRIAM, TETI GIUSEPPE,SPEZIALE PIETRO, TRIEU-CUOT PA

Abstract

STREPTOCOCCUS AGALACTIAE (GROUP BSTREPTOCOCCUS OR GBS) IS A LEADING CAUSE OFINVASIVE INFECTIONS IN NEONATES WHOSEVIRULENCE IS DEPENDENT ON ITS ABILITY TOINTERACT WITH CELLS AND HOST COMPONENTS. WEHERE CHARACTERIZED A SURFACE PROTEIN WITH ACRITICAL FUNCTION IN GBS PATHOPHYSIOLOGY. THISADHESIN, DESIGNATED PBSP, POSSESSES TWOSTREPTOCOCCAL SURFACE REPEAT DOMAINS, AMETHIONINE AND LYSINE-RICH REGION, AND A LPXTGCELL WALL-ANCHORING MOTIF. PBSP MEDIATESPLASMINOGEN (PLG) BINDING BOTH IN VITRO AND INVIVO AND WE SHOWED THAT CELL SURFACE-BOUNDPLG CAN BE ACTIVATED INTO PLASMIN BY TISSUEPLASMINOGEN ACTIVATOR TO INCREASE THEBACTERIAL EXTRACELLULAR PROTEOLYTICACTIVITY. ABSENCE OF PBSP RESULTS IN A


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DECREASED BACTERIAL TRANSMIGRATION ACROSSBRAIN ENDOTHELIAL CELLS AND IMPAIREDVIRULENCE IN A MURINE MODEL OF INFECTION. PBSPIS CONSERVED AMONG THE MAIN GBS LINEAGES ANDIS A MAJOR PLASMINOGEN ADHESIN IN NON-CC17GBS STRAINS. IMPORTANTLY, IMMUNIZATION OF MICEWITH RECOMBINANT PBSP CONFERS PROTECTIVEIMMUNITY. OUR RESULTS INDICATE THAT GBS HAVEEVOLVED DIFFERENT STRATEGIES TO RECRUIT PLGWHICH INDICATES THAT THE ABILITY TO ACQUIRECELL SURFACE PROTEOLYTIC ACTIVITY ISESSENTIAL FOR THE INVASIVENESS OF THISBACTERIUM.

Anno pubblicazione eriferimenti

MOL MICROBIOL. 2016 JUL;101(1):27-41. DOI:10.1111/MMI.13357. EPUB 2016 JUN 1.ANNO: 2016 - ISBN:

Titolo

NEUTROPHILS DIRECTLY RECOGNIZE GROUP BSTREPTOCOCCI AND CONTRIBUTE TOINTERLEUKIN-1Β PRODUCTION DURING INFECTION

Autori

NASTARAN MOHAMMADI1 , ANGELINA MIDIRI2 ,GIUSEPPE MANCUSO2 , FRANCESCO PATANÈ2 ,MARIO VENZA1 , ISABELLA VENZA1 , ANNAMARIAPASSANTINO3 , ROBERTA GALBO4 , GIUSEPPETETI1,5*, CONCETTA BENINATI2,6, CARMELO BIONDO

Abstract

PREVIOUS STUDIES HAVE SHOWN THAT THE PRO-INFLAMMATORY CYTOKINE IL-1Β HAS A CRUCIALROLE IN HOST DEFENSES AGAINST GROUP BSTREPTOCOCCUS (GBS), A FREQUENT HUMANPATHOGEN, BY RECRUITING NEUTROPHILS TOINFECTION SITES. WE EXAMINED HERE THE CELLTYPES AND MECHANISMS INVOLVED IN IL-1Β


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PRODUCTION DURING INFECTION. USING A GBS-INDUCED PERITONITIS MODEL IN MICE, WE FIRSTFOUND THAT A LARGE PROPORTION OF EXUDATECELLS CONTAIN INTRACELLULAR IL-1Β BYIMMUNOFLUORESCENCE. OF THE IL-1Β POSITIVECELLS, 82 AND 7% WERE NEUTROPHILS ANDMACROPHAGES, RESPECTIVELY, SUGGESTING THATTHE FORMER CELL TYPE MIGHT SIGNIFICANTLYCONTRIBUTE TO IL-1Β PRODUCTION. ACCORDINGLY,DEPLETION OF NEUTROPHILS WITH ANTI-LY6GANTIBODIES RESULTED IN A SIGNIFICANTREDUCTION IN THE LEVELS OF IL-1Β, BUT NOT OFTNF-Α OR IL-6. WE NEXT FOUND THAT NEUTROPHILSARE CAPABLE OF RELEASING MATURE IL-1Β ANDTNF-Α DIRECTLY IN RESPONSE TO IN VITROSTIMULATION WITH GBS. THE PRODUCTION OF PRO-IL-1Β AND TNF-Α IN THESE CELLS REQUIRED THETOLL-LIKE RECEPTOR (TLR) ADAPTOR MYD88 ANDTHE CHAPERONE PROTEIN UNC93B1, WHICH ISINVOLVED IN MOBILIZATION OF A SUBFAMILY OF TLRSTO THE ENDOSOMES. MOREOVER, PRO-IL-1ΒPROCESSING AND IL-1Β RELEASE WAS TRIGGEREDBY GBS HEMOLYSIN AND REQUIRED COMPONENTS OFTHE CANONICAL INFLAMMASOME, INCLUDINGCASPASE-1, ASC AND NLRP3. COLLECTIVELY OURFINDINGS INDICATE THAT NEUTROPHILS MAKE ASIGNIFICANT CONTRIBUTION TO IL-1Β PRODUCTIONDURING GBS INFECTION, THEREBY AMPLIFYINGTHEIR OWN RECRUITMENT. THESE CELLS DIRECTLYRECOGNIZE GBS BY MEANS OF ENDOSOMAL TLRSAND CYTOSOLIC SENSORS, LEADING TO ACTIVATIONOF THE CASPASE-1 INFLAMMASOME.


PLOS ONE | DOI:10.1371/JOURNAL.PONE.0160249AUGUST 10, 2016ANNO: 2016 - ISBN:

Titolo

A CASE OF ABSCESS AFTER BCG VACCINE IN ANIMMUNOCOMPETENT CHILD WITHOUT OTHERCLINICAL SIGNS


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Autori

D'ALEO, FRANCESCO; MANCUSO, GIUSEPPE;COSTANTINO, ANTONELLA LO PRESTI; ARENA,SALVATORE; BONANNO, ROBERTA; BIONDO,CARMELO; BENINATI, CONCETTA; MIDIRI, ANGELINA

Abstract

INTRODUCTION: BACILLE CALMETTE–GUE´ RIN (BCG),AN ATTENUATED STRAIN OF MYCOBACTERIUM BOVIS,IS A RARE CAUSE OF INFECTION, WITH FEWPUBLISHED CASES IN IMMUNOCOMPETENTINDIVIDUALS. CASE PRESENTATION: WE PRESENTTHE CASE OF A CUTANEOUS ABSCESS IN ANIMMUNOCOMPETENT INFANT RETURNING FROMMOROCCO, WHERE HE RECEIVED A BCGVACCINATION. THE ABSCESS DEVELOPED AT THESITE OF INOCULATION IN THE FOREARM (A NON-RECOMMENDED SITE) IN THE ABSENCE OFLYMPHADENOPATHY OR SYSTEMIC SIGNS. THELESION DID NOT RECUR AFTER ASPIRATION OF THEABSCESS AND FURTHER TREATMENT WAS NOTREQUIRED. CONCLUSION: INFECTIONS CAUSED BY M.BOVIS BCG MAY BE DIFFICULT TO DIAGNOSEWITHOUT SYSTEMIC SIGNS OR LYMPHADENOPATHYBUT SHOULD BE SUSPECTED IN CHILDRENRETURNING FROM REGIONS WHERE BCGVACCINATION IS WIDELY APPLIED. THE PRESENTREPORT SUGGESTS THAT ABSCESS FORMATIONAFTER BCG VACCINATION IS A CONTINUINGPROBLEM, PARTICULARLY IN TUBERCULOSIS-ENDEMIC AREAS AND WHEN RECOMMENDATIONSCONCERNING DOSAGE OR INJECTION TECHNIQUESARE NOT FOLLOWED. MOREOVER, WE HIGHLIGHTHERE THE IMPORTANCE OF COMBINING PHENOTYPICAND GENOTYPIC METHODS FOR QUICKIDENTIFICATION OF MYCOBACTERIUM BOVIS BCG INABSCESS DRAINAGE FLUIDS.


JMM CASE REPORTSANNO: 2015 - ISBN:


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Titolo

RECOGNITION OF NEISSERIA MENINGITIDIS BY THELONG PENTRAXIN PTX3 AND ITS ROLE AS ANENDOGENOUS ADJUVANT.

Autori

BOTTAZZI B;SANTINI L;SAVINO S;GIULIANI MM;DUEÑASDÍEZ AI;MANCUSO G;BENINATI C;SIRONI M;VALENTINOS;DEBAN L;GARLANDA C;TETI G;PIZZA M;RAPPUOLIR;MANTOVANI A

Abstract

LONG PENTRAXIN 3 (PTX3) IS A NON-REDUNDANTCOMPONENT OF THE HUMORAL ARM OF INNATEIMMUNITY. THE PRESENT STUDY WAS DESIGNED TOINVESTIGATE THE INTERACTION OF PTX3 WITHNEISSERIA MENINGITIDIS. PTX3 BOUND ACAPSULARMENINGOCOCCUS, NEISSERIA-DERIVED OUTERMEMBRANE VESICLES (OMV) AND 3 SELECTEDMENINGOCOCCAL ANTIGENS (GNA0667, GNA1030 ANDGNA2091). PTX3-RECOGNIZED MICROBIAL MOIETIESARE CONSERVED STRUCTURES WHICH FULFILESSENTIAL MICROBIAL FUNCTIONS. PTX3-DEFICIENTMICE HAD A LOWER ANTIBODY RESPONSE INVACCINATION PROTOCOLS WITH OMV AND CO-ADMINISTRATION OF PTX3 INCREASED THEANTIBODY RESPONSE, PARTICULARLY IN PTX3-DEFICIENT MICE. ADMINISTRATION OF PTX3REDUCED THE BACTERIAL LOAD IN INFANT RATSCHALLENGED WITH NEISSERIA MENINGITIDIS. THESERESULTS SUGGEST THAT PTX3 RECOGNIZES A SETOF CONSERVED STRUCTURES FROM NEISSERIAMENINGITIDIS AND ACTS AS ANAMPLIFIER/ENDOGENOUS ADJUVANT OF RESPONSESTO THIS BACTERIUM.


PLOS ONE. 2015 MAR 18;10(3):E0120807. DOI:


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10.1371/JOURNAL.PONE.0120807.ANNO: 2015 - ISBN:

Titolo

THE IL-1B/CXCL1/2/NEUTROPHIL AXIS MEDIATESHOST PROTECTION AGAINST GROUP BSTREPTOCOCCAL INFECTION

Autori

BIONDO, CARMELO MANCUSO, GIUSEPPE MIDIRI,ANGELINA LANZA CARICCIO, VERONICA MOHAMMADI,NASTARAN VENZA, MARIO VENZA, ISABELLA TETI,GIUSEPPE BENINATI, CONCETTA

Abstract

PREVIOUS STUDIES HAVE INDICATED THAT GROUP BSTREPTOCOCCUS (GBS), A FREQUENT HUMANPATHOGEN, POTENTLY INDUCES THE RELEASE OFIL-1Β, AN IMPORTANT MEDIATOR OF INFLAMMATORYRESPONSES. SINCE LITTLE 26 IS KNOWN ABOUT THEROLE OF THIS CYTOKINE IN GBS DISEASE, WEANALYZED THE OUTCOME OF INFECTION IN 27 IL-1Β-DEFICIENT MICE. THESE ANIMALS WERE MARKEDLYSENSITIVE TO GBS INFECTION, WITH MOST OF THEM28 DYING UNDER CHALLENGE CONDITIONS THATCAUSED NO DEATHS IN WILD TYPE CONTROL MICE.LETHALITY WAS DUE TO THE INABILITY OF THE IL-1Β-DEFICIENT MICE TO CONTROL LOCAL GBSREPLICATION AND DISSEMINATION TO TARGETORGANS, SUCH AS THE BRAIN AND THE KIDNEYS.MOREOVER, IN A MODEL OF INFLAMMATION INDUCEDBY 31 THE INTRAPERITONEAL INJECTION OF KILLEDGBS, LACK OF IL-1Β WAS ASSOCIATED WITH ASELECTIVE IMPAIRMENT 32 IN THE PRODUCTION OFTHE NEUTROPHIL CHEMOKINES CXCL1 AND CXCL2AND IN NEUTROPHIL RECRUITMENT TO THEPERITONEAL CAVITY. DECREASED BLOODNEUTROPHIL COUNTS AND IMPAIRED NEUTROPHILRECRUITMENT TO THE BRAIN AND KIDNEYS WEREALSO OBSERVED DURING GBS INFECTION IN IL-1Β-DEFICIENT MICE, CONCOMITANTLY WITH AREDUCTION IN CXCL1 AND CXCL2 TISSUE LEVELS.


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NOTABLY, THE HYPERSUSCEPTIBILITY TO GBSINFECTION OBSERVED IN THE IMMUNE DEFICIENTANIMALS WAS RECAPITULATED BY NEUTROPHILDEPLETION WITH ANTI-GR1 ANTIBODIES.COLLECTIVELY OUR DATA IDENTIFY A CYTOKINECIRCUIT THAT INVOLVES IL-1Β-INDUCEDPRODUCTION OF CXCL1 AND CXCL2 AND LEADS THERECRUITMENT OF NEUTROPHILS TO GBS INFECTIONSITES. MOREOVER OUR DATA POINT TO ANESSENTIAL ROLE OF THESE CELLS IN CONTROLLINGTHE PROGRESSION AND OUTCOME OF GBS DISEASE.


INFECT. IMMUN. 2014, 82(11):4508. DOI:10.1128/IAI.02104-14ANNO: 2014 - ISBN:

Titolo

YEAST KILLER TOXIN-LIKE CANDIDACIDAL AB6ANTIBODIES ELICITED THROUGH THE MANIPULATIONOF THE IDIOTYPIC CASCADE

Autori

L. POLONELLI; C. BENINATI; G. TETI; F. FELICI; T.CIOCIOLA; L. GIOVATI; M. SPERINDE'; C. LO PASSO; I.PERNICE; M. DOMINA; M. ARIGO`; S. PAPASERGI; G.MANCUSO; S. CONTI; W. MAGLIANI

Abstract

A MOUSE ANTI-ANTI-ANTI-IDIOTYPIC (ID) IGMMONOCLONAL ANTIBODY (MAB K20, AB4),FUNCTIONALLY MIMICKING A WYCKERHAMOMYCESANOMALUS (PICHIA ANOMALA) KILLER TOXIN (KT)CHARACTERIZED BY FUNGICIDAL ACTIVITY AGAINSTYEASTS PRESENTING SPECIFIC CELL WALLRECEPTORS (KTR) MAINLY CONSTITUTED BY B-1,3-GLUCAN, WAS PRODUCED FROM ANIMALSPRESENTING ANTI-KT ABS (AB3) FOLLOWINGIMMUNIZATION WITH A RAT IGM ANTI-ID KT-LIKE MAB


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(MAB K10, AB2). MAB K10 WAS PRODUCED BYIMMUNIZATION WITH A KTNEUTRALIZING MAB (MABKT4, AB1) BEARING THE INTERNAL IMAGE OF KTR.MAB K20, LIKEWISE MAB K10, PROVED TO BEFUNGICIDAL IN VITRO AGAINST KT-SENSITIVECANDIDA ALBICANS CELLS, AN ACTIVITYNEUTRALIZED BY MAB KT4, AND WAS CAPABLE OFBINDING TO B-1,3- GLUCAN. MAB K20 AND MAB K10COMPETED WITH EACH OTHER AND WITH KT FORBINDING TO C. ALBICANS KTR. MAB K20 WAS USED TOIDENTIFY PEPTIDE MIMICS OF KTR BY THESELECTION OF PHAGE CLONES FROM RANDOMPEPTIDE PHAGE DISPLAY LIBRARIES. USING THISSTRATEGY, FOUR PEPTIDES (TK 1-4) WERESELECTED AND USED AS IMMUNOGEN IN MICE IN THEFORM OF EITHER KEYHOLE LIMPET HEMOCYANIN(KLH) CONJUGATES OR PEPTIDE-ENCODINGMINIGENES. PEPTIDE AND DNA IMMUNIZATION COULDINDUCE SERUM ABS CHARACTERIZED BYCANDIDACIDAL ACTIVITY, WHICH WAS INHIBITED BYLAMINARIN, A SOLUBLE B-1,3-GLUCAN, BUT NOT BYPUSTULAN, A B-1,6- GLUCAN. THESE FINDINGS SHOWTHAT THE IDIOTYPIC CASCADE CAN NOT ONLYOVERCOME THE BARRIER OF ANIMAL SPECIES BUTALSO THE NATURE OF IMMUNOGENS AND THE TYPEOF TECHNOLOGY ADOPTED.


PLOS ONE. 2014 AUG 27;9(8):E105727. DOI: 10.1371ANNO: 2014 - ISBN:

Titolo

ESSENTIAL ROLE OF INTERLEUKIN-1 SIGNALING INHOST DEFENSES AGAINST GROUP BSTREPTOCOCCUS

Autori

C. BIONDO; G. MANCUSO; A. MIDIRI; G. SIGNORINO; M.DOMINA; V. LANZA CARICCIO; M. VENZA; I. VENZA; G.TETI; C. BENINATI


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Abstract

SIGNAL TRANSDUCTION VIA MYD88, AN ADAPTORPROTEIN ENGAGED BY THE TOLL-LIKE RECEPTOR(TLR) AND INTERLEUKIN-1 RECEPTOR (IL-1R) FAMILYRECEPTORS, HAS A CRUCIAL ROLE IN HOSTDEFENSES AGAINST GROUP B STREPTOCOCCUS(GBS). TO EXAMINE THE CONTRIBUTION OF IL-1RSIGNALING TO MYD88-DEPENDENT HOST DEFENSES,WE ANALYZED GBS INFECTION IN TYPE I IL-1R (IL-1RI)-DEFICIENT MICE. MOST OF THESE ANIMALSDISPLAYED CLINICAL SIGNS OF SEPSIS ANDNEUROLOGICAL DISEASE AND DIED AFTER ACHALLENGE WITH A BACTERIAL DOSE THAT DID NOTCAUSE ILLNESS OR DEATH IN ANY OF THE WILD-TYPEANIMALS. MOREOVER, BACTERIAL NUMBERS IN THEBLOOD AND BRAINS OF THE IMMUNODEFECTIVE MICEWERE CONSIDERABLY INCREASED. THE ABILITY OFBLOOD LEUKOCYTES OR BONE MARROW-DERIVEDMACROPHAGES TO KILL GBS IN VITRO WAS NOTAFFECTED BY A LACK OF IL-1RI. HOWEVER, IT WASFOUND IN A NEWLY DEVELOPED MODEL OF GBS-INDUCED PERITONEAL INFLAMMATION THAT IL-1SIGNALING SELECTIVELY PROMOTED THEPRODUCTION OF THE CHEMOKINES KC AND MIP-1AND NEUTROPHIL RECRUITMENT. MOREOVER, THESECRETION OF KC AND MIP-1, BUT NOT TUMORNECROSIS FACTOR ALPHA, BY PERITONEALMACROPHAGES STIMULATED WITH GBS WASSIGNIFICANTLY DECREASED IN THE ABSENCE OFIL-1RI. ACCORDINGLY, THE NUMBER OF NEUTROPHILSIN THE BLOOD AND THE CONCENTRATION OFMYELOPEROXIDASE, A NEUTROPHIL MARKER, ININFECTED ORGANS WERE SEVERELY REDUCED INTHE IMMUNODEFECTIVE MICE DURING GBS DISEASE,CONCOMITANTLY WITH A REDUCTION IN TISSUE KCAND MIP-1 LEVELS. IN CONCLUSION, IL-1RI PLAYS ACRUCIAL ROLE IN HOST DEFENSES AGAINST GBS BYINDUCING THE HIGH-LEVEL PRODUCTION OFCHEMOKINES AND THE SUBSEQUENT RECRUITMENTOF NEUTROPHILIC POLYMORPHONUCLEARLEUKOCYTES TO INFECTION SITES. IMPORTANCEGROUP B STREPTOCOCCUS (GBS) IS A SERIOUS ANDFREQUENT HUMAN PATHOGEN. EXPERIMENTALINFECTION WITH THIS BACTERIUM HAS BEEN WIDELYUSED TO UNDERSTAND THE MECHANISM WHEREBYTHE BODY’S FIRST LINE OF DEFENSE, REPRESENTEDBY CELLS AND MOLECULES OF THE INNATE IMMUNE


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SYSTEM, FIGHTS INFECTIONS. IN BOTH HUMANS ANDMICE, DEFECTIVE FUNCTION OF THE ADAPTORMOLECULE MYD88 HAS BEEN ASSOCIATED WITHEXTREME SUSCEPTIBILITY TO INFECTION BY GBSAND OTHER EXTRACELLULAR BACTERIA. WE SHOWHERE THAT LACK OF SIGNALING BY INTERLEUKIN-1(IL-1) CYTOKINES CAN LARGELY, ALTHOUGH NOTCOMPLETELY, EXPLAIN THE INCREASEDSUSCEPTIBILITY TO INFECTION OBSERVED IN THEABSENCE OF MYD88 FUNCTION. WE SHOW, INPARTICULAR, THAT IL-1 SIGNALING THROUGH THE IL-1RECEPTOR PROMOTES THE PRODUCTION OF THELEUKOCYTE ATTRACTANT CHEMOKINES KC ANDMIP-1 AND RECRUITMENT OF NEUTROPHILS TO GBSINFECTION SITES, THEREBY ENABLING THESELEUKOCYTES TO CLEAR THE INFECTION. OURFINDINGS INDICATE THAT STIMULATION OF IL-1SIGNALING MAY BE USEFUL AS AN ALTERNATIVETHERAPEUTIC STRATEGY TO TREAT GBSINFECTIONS.


MBIO. 2014 SEP 9;5(5):E01428-14. DOI:10.1128/MBIO.01428-14.ANNO: 2014 - ISBN:

Titolo

THE IL-1Β/CXCL1/2/NEUTROPHIL AXIS MEDIATESHOST PROTECTION AGAINST GROUP BSTREPTOCOCCAL INFECTION.

Autori

CARMELO, BIONDO; GIUSEPPE, MANCUSO; ANGELINA,MIDIRI; GIACOMO, SIGNORINO; MARIA, DOMINA;VERONICA, LANZA CARICCIO; NASTARAN,MOHAMMADI; MARIO, VENZA; ISABELLA, VENZA;GIUSEPPE, TETI; CONCETTA, BENINATI

Abstract


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PREVIOUS STUDIES HAVE INDICATED THAT GROUP BSTREPTOCOCCUS (GBS), A FREQUENT HUMANPATHOGEN, POTENTLY INDUCES THE RELEASE OFINTERLEUKIN-1 (IL-1), AN IMPORTANT MEDIATOR OFINFLAMMATORY RESPONSES. SINCE LITTLE ISKNOWN ABOUT THE ROLE OF THIS CYTOKINE IN GBSDISEASE, WE ANALYZED THE OUTCOME OFINFECTION IN IL-1-DEFICIENT MICE. THESE ANIMALSWERE MARKEDLY SENSITIVE TO GBS INFEC- TION,WITH MOST OF THEM DYING UNDER CHALLENGECONDITIONS THAT CAUSED NO DEATHS IN WILD-TYPECONTROL MICE. LETHALITY WAS DUE TO THEINABILITY OF THE IL-1-DEFICIENT MICE TO CONTROLLOCAL GBS REPLICATION AND DISSEMINATION TOTARGET ORGANS, SUCH AS THE BRAIN AND THEKIDNEYS. MOREOVER, IN A MODEL OF INFLAMMATIONINDUCED BY THE INTRAPERITONEAL INJECTION OFKILLED GBS, A LACK OF IL-1 WAS ASSOCIATED WITHSELECTIVE IMPAIRMENT IN THE PRODUCTION OF THENEUTROPHIL CHEMOKINES CXCL1 AND CXCL2 AND INNEUTROPHIL RECRUITMENT TO THE PERITONEALCAVITY. DECREASED BLOOD NEUTROPHIL COUNTSAND IMPAIRED NEUTROPHIL RECRUITMENT TO THEBRAIN AND KIDNEYS WERE ALSO OBSERVED DURINGGBS INFECTION IN IL-1-DEFICIENT MICECONCOMITANTLY WITH A REDUCTION IN CXCL1 ANDCXCL2 TISSUE LEVELS. NOTABLY, THEHYPERSUSCEPTIBILITY TO GBS INFECTIONOBSERVED IN THE IMMUNE-DEFICIENT ANIMALS WASRECAPITULATED BY NEUTROPHIL DEPLETION WITHANTI-GR1 ANTIBODIES. COLLECTIVELY, OUR DATAIDENTIFY A CYTOKINE CIRCUIT THAT INVOLVES IL-1-INDUCED PRO- DUCTION OF CXCL1 AND CXCL2 ANDLEADS THE RECRUITMENT OF NEUTROPHILS TO GBSINFECTION SITES. MOREOVER, OUR DATA POINT TOAN ESSENTIAL ROLE OF THESE CELLS INCONTROLLING THE PROGRESSION AND OUTCOME OFGBS DISEASE.


INFECT IMMUN. 2014 NOV;82(11):4508-17. DOI:10.1128/IAI.02104-14.ANNO: 2014 - ISBN:


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Titolo

ROLE OF TLR13 IN INNATE IMMUNE RECOGNITION OFGROUP B STREPTOCOCCI

Autori

G. SIGNORINO; N. MOHAMMADI; F. PATANÈ; M.BUSCETTA; M. VENZA; I. VENZA; G MANCUSO; A.MIDIRI; L. ALEXOPOULOU; G. TETI; C. BIONDO; C.BENINATI

Abstract

MURINE TLR13, AN ENDOSOMAL RECEPTOR THAT ISNOT PRESENT IN HUMANS, IS ACTIVATED BY ANUNMETHYLATED MOTIF PRESENT IN THE LARGERIBOSOME SUBUNIT OF BACTERIAL RNA (23S RRNA).LITTLE IS KNOWN, HOWEVER, OF THE IMPACT OFTLR13 ON ANTIBACTERIAL HOST DEFENSES. HEREWE EXAMINED THE ROLE OF THIS RECEPTOR IN THECONTEXT OF INFECTION INDUCED BY THE MODELPATHOGEN GROUP B STREPTOCOCCUS (GBS). TOTHIS END, WE USED BACTERIAL STRAINS MASKEDFROM TLR13 RECOGNITION BY VIRTUE OFCONSTITUTIVE EXPRESSION OF ERMCMETHYLTRANSFERASE, WHICH RESULTS INDIMETHYLATION OF THE 23S RRNA MOTIF AT ACRITICAL ADENINE RESIDUE. WE FOUND THAT TLR13-MEDIATED RRNA RECOGNITION IS REQUIRED FOROPTIMAL INDUCTION OF TUMOR NECROSIS FACTOR-ΑAND NITROUS OXIDE IN DENDRITIC CELL ANDMACROPHAGE CULTURES STIMULATED WITH HEATKILLED BACTERIA 33 OR PURIFIED BACTERIAL RNA.HOWEVER, TLR13-DEPENDENT RECOGNITION WASREDUNDANT WHEN USING LIVE 34 BACTERIA AS ASTIMULUS. MOREOVER, MASKING BACTERIAL RRNAFROM TLR13 RECOGNITION DID NOT INCREASE THE35 ABILITY OF GBS TO AVOID HOST DEFENSES ANDREPLICATE IN VIVO. IN CONTRAST, INCREASEDSUSCEPTIBILITY TO 36 INFECTION WAS OBSERVEDUNDER CONDITIONS IN WHICH SIGNALING BY ALLENDOSOMAL TLRS IS ABOLISHED I.E. IN 37 MICE WITHA LOSS-OF-FUNCTION MUTATION IN THE CHAPERONEPROTEIN UNC93B1. OUR DATA LEND SUPPORT TO THE


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38 CONCLUSION THAT TLR13 PARTICIPATES IN GBSRECOGNITION, ALTHOUGH BLOCKADE OF THEFUNCTION OF THIS 39 RECEPTOR CAN BECOMPENSATED FOR BY OTHER ENDOSOMAL TLRS.LACK OF SELECTIVE PRESSURE BY BACTERIAL 40INFECTIONS MIGHT EXPLAIN THE EVOLUTIONARYLOSS OF TLR13 IN HUMANS. HOWEVER, FURTHERSTUDIES USING 41 DIFFERENT BACTERIAL SPECIESARE NEEDED TO PROVE THIS HYPOTHESIS.


INFECT IMMUN. 2014 DEC;82(12):5013-22. DOI:10.1128/IAI.02282-14.ANNO: 2014 - ISBN:

Titolo

PROTOTYPIC LONG PENTRAXIN PTX3 IS PRESENT INBREAST MILK, SPREADS IN TISSUES, AND PROTECTSNEONATE MICE FROM PSEUDOMONAS AERUGINOSALUNG INFECTION.

Autori

JAILLON S, MANCUSO G, HAMON Y, BEAUVILLAIN C,COTICI V, MIDIRI A, BOTTAZZI B, NEBULONI M,GARLANDA C, FRÉMAUX I, GAUCHAT JF, DESCAMPS P,BENINATI C, MANTOVANI A, JEANNIN P, DELNESTE Y.

Abstract

NEWBORNS AND INFANTS PRESENT A HIGHERSUSCEPTIBILITY TO INFECTION THAN ADULTS, AVULNERABILITY ASSOCIATED WITH DEFICIENCIES INBOTH THE INNATE AND ADAPTIVE IMMUNE SYSTEMS.INNATE IMMUNE RECEPTORS ARE SENSORSINVOLVED IN THE RECOGNITION AND ELIMINATION OFMICROBES THAT PLAY A PIVOTAL ROLE AT THEINTERFACE BETWEEN INNATE AND ADAPTIVEIMMUNITY. PENTRAXIN 3 (PTX3), THE PROTOTYPICLONG PENTRAXIN, IS A SOLUBLE PATTERNRECOGNITION RECEPTOR INVOLVED IN THE


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INITIATION OF PROTECTIVE RESPONSES AGAINSTSELECTED PATHOGENS. BECAUSE NEONATES AREGENERALLY RESISTANT TO THESE PATHOGENS, WESUSPECTED THAT PTX3 MAY BE PROVIDED BY AMATERNAL SOURCE DURING THE EARLY LIFE TIMES.WE OBSERVED THAT HUMAN COLOSTRUM CONTAINSHIGH LEVELS OF PTX3, AND THAT MAMMARYEPITHELIAL CELL AND CD11B(+) MILK CELLSCONSTITUTIVELY PRODUCE PTX3. INTERESTINGLY,PTX3 GIVEN ORALLY TO NEONATE MICE WAS RAPIDLYDISTRIBUTED IN DIFFERENT ORGANS, AND PTX3INGESTED DURING LACTATION WAS DETECTED INNEONATES. FINALLY, WE OBSERVED THAT ORALLYADMINISTERED PTX3 PROVIDED PROTECTIONAGAINST PSEUDOMONAS AERUGINOSA LUNGINFECTION IN NEONATE MICE. THEREFORE,BREASTFEEDING CONSTITUTES, DURING THE EARLYLIFE TIMES, AN IMPORTANT SOURCE OF PTX3, WHICHACTIVELY PARTICIPATES IN THE PROTECTION OFNEONATES AGAINST INFECTIONS. IN ADDITION,THESE RESULTS SUGGEST THAT PTX3 MIGHTREPRESENT A THERAPEUTIC TOOL FOR TREATINGNEONATAL INFECTIONS AND SUPPORT THE VIEWTHAT BREASTFEEDING HAS BENEFICIAL EFFECTS ONTHE NEONATES' HEALTH.


J IMMUNOL. 2013 AUG 15;191(4):1873-82. DOI:10.4049/JIMMUNOL.1201642ANNO: 2013 - ISBN:

Titolo

IMMUNOGENIC PROPERTIES OF STREPTOCOCCUSAGALACTIAE FBSA FRAGMENTS.

Autori

PAPASERGI, SALVATORE LANZA CARICCIO, VERONICAD'ALIBERTI, DEBORAH BIONDO, CARMELO MANCUSO,GIUSEPPE MIDIRI, ANGELINA TETI, GIUSEPPEBENINATI, CONCETTA


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Abstract

SEVERAL SPECIES OF GRAM-POSITIVE BACTERIACAN AVIDLY BIND SOLUBLE AND SURFACE-ASSOCIATED FIBRINOGEN (FNG), A PROPERTY THATIS CONSIDERED IMPORTANT IN THE PATHOGENESISOF HUMAN INFECTIONS. TO GAIN INSIGHTS INTO THEMECHANISM BY WHICH GROUP B STREPTOCOCCUS(GBS), A FREQUENT NEONATAL PATHOGEN,INTERACTS WITH FNG, WE HAVE SCREENED TWOPHAGE DISPLAYED GENOMIC GBS LIBRARIES. ALL OFTHE FNG-BINDING PHAGE CLONES CONTAINEDINSERTS ENCODING FRAGMENTS OF FBSA, APROTEIN DISPLAYING MULTIPLE REPEATS. SINCE THEFUNCTIONAL ROLE OF THIS PROTEIN IS ONLYPARTIALLY UNDERSTOOD, REPRESENTATIVEFRAGMENTS WERE RECOMBINANTLY EXPRESSEDAND ANALYZED FOR FNG BINDING AFFINITY ANDABILITY TO INDUCE IMMUNE PROTECTION AGAINSTGBS INFECTION. MATERNAL IMMUNIZATION WITH6PGST, A FRAGMENT CONTAINING FIVE REPEATS,SIGNIFICANTLY PROTECTED MOUSE PUPS AGAINSTLETHAL GBS CHALLENGE AND THESE PROTECTIVEEFFECTS COULD BE RECAPITULATED BYADMINISTRATION OF ANTI-6PGST SERUM FROMADULT ANIMALS. NOTABLY, A MONOCLONAL ANTIBODYTHAT WAS CAPABLE OF NEUTRALIZING FNG BINDINGBY 6PGST, BUT NOT A NON-NEUTRALIZING ANTIBODY,COULD SIGNIFICANTLY PROTECT PUPS AGAINSTLETHAL GBS CHALLENGE. THESE DATA SUGGESTTHAT FBSA-FNG INTERACTION PROMOTES GBSPATHOGENESIS AND THAT BLOCKING SUCHINTERACTION IS A VIABLE STRATEGY TO PREVENTOR TREAT GBS INFECTIONS.


PLOS ONE. 2013 SEP 24;8(9):E75266. DOI:10.1371/JOURNAL.PONE.0075266ANNO: 2013 - ISBN:

Titolo

SECONDARY HEMOPHAGOCYTIC


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LYMPHOHISTIOCYTOSIS IN ZOONOSES. ASYSTEMATIC REVIEW

Autori

A., CASCIO; L. M., PERNICE; G., BARBERI; D., DELFINO;C., BIONDO; C., BENINATI; G., MANCUSO; A. J.,RODRIGUEZ-MORALES; C., IARIA

Abstract

HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS (HLH) IS ARARE SYNDROME THAT IS OFTEN FATAL DESPITETREATMENT. IT IS CAUSED BY A DYSREGULATION INNATURAL KILLER T-CELL FUNCTION, RESULTING INACTIVATION AND PROLIFERATION OF HISTIOCYTESWITH UNCONTROLLED HEMOPHAGOCYTOSIS ANDCYTOKINES OVERPRODUCTION. THE SYNDROME ISCHARACTERIZED BY FEVER, HEPATOSPLENOMEGALY,CYTOPENIAS, LIVER DYSFUNCTION, ANDHYPERFERRITINEMIA. HLH CAN BE EITHER PRIMARY,WITH A GENETIC AETIOLOGY, OR SECONDARY,ASSOCIATED WITH MALIGNANCIES, AUTOIMMUNEDISEASES, OR INFECTIONS. AIM: TO FOCUS ONSECONDARY HLH COMPLICATING ZOONOTICDISEASES. MATERIALS AND METHODS: PUBMEDSEARCH OF HUMAN CASES OF HLH OCCURRINGDURING ZOONOTIC DISEASES WAS PERFORMEDCOMBINING THE TERMS (HAEMOPHAGOCYTIC ORHAEMOPHAGOCYTOSIS OR HEMOPHAGOCYTOSIS ORHEMOPHAGOCYTIC OR ERYTHROPHAGOCYTOSIS ORMACROPHAGE ACTIVATION SYNDROME) WITH EACHONE OF THE ETIOLOGICAL AGENTS OF ZOONOSES.RESULTS: AMONG BACTERIAL DISEASES, MOSTPAPERS REPORTED CASES OCCURRING DURINGBRUCELLOSIS, RICKETTSIAL DISEASES AND QFEVER. REGARDING VIRAL DISEASES, MOST OF THECASES WERE REPORTED IN PATIENTS WITH AVIANINFLUENZA A SUBTYPE H5N1. AMONG THEPROTOZOAN ZOONOSES, MOST OF THE CASES WEREREPORTED IN PATIENTS WITH VISCERALLEISHMANIASIS. REGARDING ZOONOTIC FUNGI, MOSTOF THE CASES WERE REPORTED IN AIDS PATIENTWITH HISTOPLASMOSIS. NO CASES OF SECONDARYHLH WERE REPORTED IN PATIENT WITH ZOONOTICHELMINTHES. CONCLUSIONS: ZOONOTIC DISEASESARE AN IMPORTANT CAUSE OF HLH. SECONDARY HLH


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CAN DELAY THE CORRECT DIAGNOSIS OF THEZOONOTIC DISEASE, AND CAN CONTRIBUTE TO ANADVERSE OUTCOME.


EUR REV MED PHARMACOL SCI. 2012OCT;16(10):1324-37. REVIEWANNO: 2012 - ISBN:

Titolo

ACTIVATION OF THE NLRP3 INFLAMMASOME BYGROUP B STREPTOCOCCI.

Autori

COSTA A; GUPTA R; SIGNORINO G; MALARA A;CARDILE F; BIONDO C; MIDIRI A; GALBO R; TRIEU-CUOT P; PAPASERGI S; TETI G; HENNEKE P; MANCUSOG; GOLENBOCK DT; BENINATI C.

Abstract

GROUP B STREPTOCOCCUS (GBS) IS A FREQUENTAGENT OF LIFE-THREATENING SEPSIS ANDMENINGITIS IN NEONATES AND ADULTS WITHPREDISPOSING CONDITIONS. WE TESTED THEHYPOTHESIS THAT ACTIVATION OF THEINFLAMMASOME, AN INFLAMMATORY SIGNALINGCOMPLEX, IS INVOLVED IN HOST DEFENSES AGAINSTTHIS PATHOGEN. WE SHOW IN THIS STUDY THATMURINE BONE MARROW-DERIVED CONVENTIONALDENDRITIC CELLS RESPONDED TO GBS BYSECRETING IL-1Β AND IL-18. IL-1Β RELEASEREQUIRED BOTH PRO-IL-1Β TRANSCRIPTION ANDCASPASE-1-DEPENDENT PROTEOLYTIC CLEAVAGE OFINTRACELLULAR PRO-IL-1Β. DENDRITIC CELLSLACKING THE TLR ADAPTOR MYD88, BUT NOT THOSELACKING TLR2, WERE UNABLE TO PRODUCE PRO-IL-1Β MRNA IN RESPONSE TO GBS. PRO-IL-1ΒCLEAVAGE AND SECRETION OF THE MATURE IL-1ΒFORM DEPENDED ON THE NOD-LIKE RECEPTOR


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FAMILY, PYRIN DOMAIN CONTAINING 3 (NLRP3)SENSOR AND THE APOPTOSIS-ASSOCIATED SPECK-LIKE PROTEIN CONTAINING A CASPASE ACTIVATIONAND RECRUITMENT DOMAIN ADAPTOR. MOREOVER,ACTIVATION OF THE NLRP3 INFLAMMASOMEREQUIRED GBS EXPRESSION OF Β-HEMOLYSIN, ANIMPORTANT VIRULENCE FACTOR. WE FURTHERFOUND THAT MICE LACKING NLRP3, APOPTOSIS-ASSOCIATED SPECK-LIKE PROTEIN, OR CASPASE-1WERE CONSIDERABLY MORE SUSCEPTIBLE TOINFECTION THAN WILD-TYPE MICE. OUR DATA LINKTHE PRODUCTION OF A MAJOR VIRULENCE FACTORBY GBS WITH THE ACTIVATION OF A HIGHLYEFFECTIVE ANTI-GBS RESPONSE TRIGGERED BY THENLRP3 INFLAMMASOME.


J IMMUNOL. 2012 FEB 15;188(4):1953-60. DOI:10.4049/JIMMUNOL.1102543ANNO: 2012 - ISBN:

Titolo

THE ROLE OF ENDOSOMAL TOLL-LIKE RECEPTORS INBACTERIAL RECOGNITION

Autori

BIONDO, CARMELO MANCUSO, GIUSEPPE BENINATI,CONCETTA IARIA, CHIARA ROMEO, ORAZIO CASCIO,ANTONIO TETI, GIUSEPPE

Abstract

INFECTIONS CAUSED BY EXTRACELLULAR GRAMPOSITIVE BACTERIA ARE STILL A MAJOR HEALTHPROBLEMS. BETTER UNDERSTANDING OF THEMECHANISMS UNDERLYING IMMUNE RESPONSES TOTHESE ORGANISMS IS KEY TO DEVELOPPHARMACOLOGICAL AGENTS, INCLUDING VACCINES,TO CONTROL THESE INFECTIONS. OBJECTIVE ANDPERSPECTIVES: THE OBJECTIVE OF THIS REVIEW IS


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TO HIGHLIGHT THE IMPORTANCE OF NUCLEIC ACID-SENSING, INTRACELLULAR TOLL-LIKE RECEPTORS ININNATE IMMUNE RECOGNITION AND IN HOSTDEFENSES AGAINST EXTRACELLULAR BACTERIA.CONCLUSIONS: TOLL-LIKE RECEPTORS 7 AND 9 HAVEA MAJOR ROLE IN INDUCING HOST-PROTECTIVE TYPEI INTERFERON RESPONSES IN CONVENTIONALDENDRITIC CELLS IN RESPONSE TO STREPTOCOCCIAND OTHER EXTRACELLULAR GRAM POSITIVEBACTERIA. MOREOVER AN AS YET UNIDENTIFIEDMYD88-DEPENDENT RECEPTOR IS LIKELYRESPONSIBLE FOR PROINFLAMMATORY CYTOKINEINDUCTION IN RESPONSE TO THESE PATHOGENS.


EUR REV MED PHARMACOL SCI. 2012OCT;16(11):1506-12.ANNO: 2012 - ISBN:

Titolo

RECOGNITION OF FUNGAL RNA BY TLR7 HAS A NON-REDUNDANT ROLE IN HOST DEFENSE AGAINSTEXPERIMENTAL CANDIDIASIS.

Autori

BIONDO, CARMELO MIDIRI, ANGELINA GALBO,ROBERTA PAPASERGI, SALVATORE PUGLIESE,MICHELA TETI, GIUSEPPE MANCUSO, GIUSEPPEBENINATI, CONCETTA

Abstract

DESPITE CONVINCING EVIDENCE FOR INVOLVEMENTOF MEMBERS OF THE TOLL-LIKE RECEPTOR (TLR)FAMILY IN FUNGAL RECOGNITION, LITTLE IS KNOWNOF THE FUNCTIONAL ROLE OF INDIVIDUAL TLRS INANTIFUNGAL DEFENSES. WE FOUND HERE THAT TLR7WAS PARTIALLY REQUIRED FOR THE INDUCTION OFIL-12 (IL-12P70) BY CANDIDA ALBICANS ORSACCHAROMYCES CEREVISIAE. MOREOVER, THE


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IL-12P70 RESPONSE WAS COMPLETELY ABROGATEDIN CELLS FROM 3D MICE, WHICH ARE UNABLE TOMOB-ILIZE TLRS TO ENDOSOMAL COMPARTMENTS,AS WELL AS IN CELLS FROM MICE LACKING EITHERTHE TLR ADAPTOR MYD88 OR THE IRF1TRANSCRIPTION FACTOR. NOTABLY, PURIFIEDFUNGAL RNA RECAPITULATED IL-12P70 INDUCTIONBY WHOLE YEAST. ALTHOUGH RNA COULD ALSOINDUCE MODERATE TLR7-DEPENDENT IL-23 ANDTUMOR NECROSIS FACTOR-ALPHA (TNF-A)SECRETION, TLR7 AND OTHER ENDOSOMAL TLRSWERE REDUNDANT FOR IL-23 OR TNF-A INDUCTIONBY WHOLE FUNGI. IMPORTANTLY, MICE LACKING TLR7OR IRF1 WERE HYPERSUSCEPTIBLE TO SYSTEMIC C.ALBICANS INFECTION. OUR DATA SUGGEST THAT IRF1IS DOWNSTREAM OF A NOVEL, NONREDUNDANTFUNGAL RECOGNITION PATHWAY THAT HAS RNA AS AMAJOR TARGET AND REQUIRES PHAGOSOMALRECRUITMENT OF INTRACELLULAR TLRS. THISPATHWAY DIFFERS FROM THOSE INVOLVED IN IL-23OR TNF-A RESPONSES, WHICH WE SHOW HERE TOBE INDEPENDENT FROM TRANSLOCATION OFINTRACELLULAR TLRS, PHAGOCYTOSIS, ORPHAGOSOMAL ACIDIFICATION.


EUR J IMMUNOL. 2012 OCT;42(10):2632-43. DOI:10.1002/EJI.201242532.ANNO: 2012 - ISBN:

Titolo

IMMUNIZATION WITH THE RRGB321 FUSION PROTEINPROTECTS MICE AGAINST BOTH HIGH AND LOWPILUS-EXPRESSING STREPTOCOCCUS PNEUMONIAEPOPULATIONS.

Autori

MOSCHIONI M, DE ANGELIS G, HARFOUCHE C,BIZZARRI E, FILIPPINI S, MORI E, MANCUSO G, DOROF, BAROCCHI MA, RUGGIERO P, MASIGNANI V.


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Abstract

RRGB321, A FUSION PROTEIN OF THE THREESTREPTOCOCCUS PNEUMONIAE PILUS-1 BACKBONERRGB VARIANTS, IS PROTECTIVE IN VIVO AGAINSTPILUS ISLET 1 (PI-1) POSITIVE PNEUMOCOCCI. INADDITION, ANTIBODIES TO RRGB321 MEDIATE ACOMPLEMENT-DEPENDENT OPSONOPHAGOCYTOSISOF PI-1 POSITIVE STRAINS AT LEVELS COMPARABLETO THOSE OBTAINED WITH ANTISERA AGAINSTGLYCOCONJUGATE VACCINES. IN THEPNEUMOCOCCUS, PILUS-1 DISPLAYS A BIPHASICEXPRESSION PATTERN, WITH DIFFERENTPROPORTIONS OF TWO BACTERIAL PHENOTYPES,ONE EXPRESSING AND ONE NOT EXPRESSING THEPILUS-1. THESE TWO POPULATIONS CAN BE STABLYSEPARATED IN VITRO GIVING RISE TO THE ENRICHEDHIGH (H) AND LOW (L) PILUS EXPRESSINGPOPULATIONS. IN THIS WORK WE DEMONSTRATETHAT: (I) THE OPSONOPHAGOCYTIC KILLINGMEDIATED IN VITRO BY RRGB321ANTISERA ISSTRICTLY DEPENDENT ON THE PILUS EXPRESSIONRATIO OF THE STRAIN USED; (II) DURING THEOPSONOPHAGOCYTOSIS ASSAY PILUS-EXPRESSINGPNEUMOCOCCI ARE SELECTIVELY KILLED, AND (III)NO SWITCH TOWARDS THE PILUS NON-EXPRESSINGPHENOTYPE CAN BE OBSERVED. FURTHERMORE, INSEPSIS AND PNEUMONIA MODELS, MICE IMMUNIZEDWITH RRGB321 ARE SIGNIFICANTLY PROTECTEDAGAINST CHALLENGE WITH EITHER THE H OR THE LPILUS-EXPRESSING POPULATION OF STRAINSREPRESENTATIVE OF THE THREE RRGB VARIANTS.THIS SUGGESTS THAT THE PILUS-1 EXPRESSION ISNOT DOWN-REGULATED, AND ALSO THAT THEEXPRESSION OF THE PILUS-1 COULD BE UP-REGULATED IN VIVO. IN CONCLUSION, THESE DATAPROVIDE EVIDENCE THAT RRGB321 IS PROTECTIVEAGAINST PI-1 POSITIVE STRAINS REGARDLESS OFTHEIR PILUS EXPRESSION LEVEL, AND SUPPORT THERATIONALE FOR THE INCLUSION OF THIS FUSIONPROTEIN INTO A MULTI-COMPONENT PROTEIN-BASEDPNEUMOCOCCAL VACCINE.



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VACCINE. 2012 FEB 8;30(7):1349-56. DOI:10.1016/J.VACCINE.2011.12.080.ANNO: 2012 - ISBN:

Titolo

RRGB321, A FUSION PROTEIN OF THE THREEVARIANTS OF THE PNEUMOCOCCAL PILUS BACKBONERRGB, IS PROTECTIVE IN VIVO AND ELICITS OPSONICANTIBODIES.

Autori

HARFOUCHE C, FILIPPINI S, GIANFALDONI C,RUGGIERO P, MOSCHIONI M, MACCARI S, PANCOTTOL, ARCIDIACONO L, GALLETTI B, CENSINI S, MORI E,GIULIANI M, FACCIOTTI C, CARTOCCI E, SAVINO S,DORO F, PALLAORO M, NOCADELLO S, MANCUSO G,HASTON M, GOLDBLATT D, B

Abstract

STREPTOCOCCUS PNEUMONIAE PILUS 1 IS PRESENTIN 30 TO 50% OF INVASIVE DISEASE-CAUSINGSTRAINS AND IS COMPOSED OF THREE SUBUNITS:THE ADHESIN RRGA, THE MAJOR BACKBONE SUBUNITRRGB, AND THE MINOR ANCILLARY PROTEIN RRGC.RRGB EXISTS IN THREE DISTINCT GENETIC VARIANTSAND, WHEN USED TO IMMUNIZE MICE, INDUCES ANIMMUNE RESPONSE SPECIFIC FOR EACH VARIANT. TOGENERATE AN ANTIGEN ABLE TO PROTECT AGAINSTTHE INFECTION CAUSED BY ALL PILUS-POSITIVE S.PNEUMONIAE STRAINS, WE ENGINEERED A FUSIONPROTEIN CONTAINING THE THREE RRGB VARIANTS(RRGB321). RRGB321 ELICITED ANTIBODIES AGAINSTPROTEINS FROM ORGANISMS IN THE THREE CLADESAND PROTECTED MICE AGAINST CHALLENGE WITHPILIATED PNEUMOCOCCAL STRAINS. RRGB321ANTISERA MEDIATED COMPLEMENT-DEPENDENTOPSONOPHAGOCYTOSIS OF PILIATED STRAINS ATLEVELS COMPARABLE TO THOSE ACHIEVED WITHTHE PCV7 GLYCOCONJUGATE VACCINE. THESERESULTS SUGGEST THAT A VACCINE COMPOSED OFRRGB321 HAS THE POTENTIAL TO COVER 30% OR


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MORE OF ALL PNEUMOCOCCAL STRAINS ANDSUPPORT THE INCLUSION OF THIS FUSION PROTEININ A MULTICOMPONENT VACCINE AGAINST S.PNEUMONIAE.


INFECT IMMUN. 2012 JAN;80(1):451-60. DOI:10.1128/IAI.05780-11.ANNO: 2012 - ISBN:

Titolo

PROTECTIVE ACTIVITY OF STREPTOCOCCUSPNEUMONIAE SPR1875 PROTEIN FRAGMENTSIDENTIFIED USING A PHAGE DISPLAYED GENOMICLIBRARY.

Autori

CARDACI, ANGELA PAPASERGI, SALVATORE MIDIRI,ANGELINA MANCUSO, GIUSEPPE LANZA CARICCIO,VERONICA MANDANICI, FRANCESCA GALBO,ROBERTA LO PASSO, CARLA PERNICE, IDA BIONDO,CARMELO TETI, GIUSEPPE FELICI, FRANCO BENINATI,CONCETTA

Abstract

THERE IS CONSIDERABLE INTEREST INPNEUMOCOCCAL PROTEIN ANTIGENS CAPABLE OFINDUCING SEROTYPE-INDEPENDENTIMMUNOPROTECTION AND OF IMPROVING, THEREBY,EXISTING VACCINES. WE REPORT HERE ON THEIMMUNOGENIC PROPERTIES OF A NOVEL SURFACEANTIGEN ENCODED BY ORF SPR1875 IN THE R6STRAIN GENOME. AN ANTIGENIC FRAGMENTENCODED BY SPR1875, DESIGNATED R4, WASIDENTIFIED USING A STREPTOCOCCUS PNEUMONIAEPHAGE DISPLAYED GENOMIC LIBRARY AFTERSELECTION WITH A HUMAN CONVALESCENT SERUM.IMMUNOFLUORESCENCE ANALYSIS WITH ANTI-R4ANTISERA SHOWED THAT SPR1875 WAS EXPRESSED


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ON THE SURFACE OF STRAINS BELONGING TODIFFERENT SEROTYPES. MOREOVER, THE GENE WASPRESENT WITH LITTLE SEQUENCE VARIABILITY IN 27DIFFERENT PNEUMOCOCCAL STRAINS ISOLATEDWORLDWIDE. A MUTANT LACKING SPR1875 WASCONSIDERABLY LESS VIRULENT THAN THE WILDTYPE D39 STRAIN IN AN INTRAVENOUS MOUSE MODELOF INFECTION. MOREOVER, IMMUNIZATION WITH THER4 RECOMBINANT FRAGMENT, BUT NOT WITH THEWHOLE SPR1875 PROTEIN, INDUCED SIGNIFICANTPROTECTION AGAINST SEPSIS IN MICE. LACK OFPROTECTION AFTER IMMUNIZATION WITH THEWHOLE PROTEIN WAS RELATED TO THE PRESENCEOF IMMUNODOMINANT, NON-PROTECTIVE EPITOPESLOCATED OUTSIDE OF THE R4 FRAGMENT. INCONCLUSION, OUR DATA INDICATE THAT SPR1875HAS A ROLE IN PNEUMOCOCCAL VIRULENCE AND ISIMMUNOGENIC. AS THE R4 FRAGMENT CONFERREDIMMUNOPROTECTION FROM EXPERIMENTAL SEPSIS,SELECTED ANTIGENIC FRAGMENTS OF SPR1875 MAYBE USEFUL FOR THE DEVELOPMENT OF APNEUMOCOCCAL PROTEIN-BASED VACCINE.


PLOS ONE. 2012;7(5):E36588. DOI:10.1371/JOURNAL.PONE.0036588ANNO: 2012 - ISBN:

Titolo

RECOGNITION OF YEAST NUCLEIC ACIDS TRIGGERSA HOST-PROTECTIVE TYPE I INTERFERONRESPONSE.

Autori

BIONDO C, SIGNORINO G, COSTA A, MIDIRI A, GERACEE, GALBO R, BELLANTONI A, MALARA A, BENINATI C,TETI G, MANCUSO G.

Abstract


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ALTHOUGH TYPE I INTERFERONS (IFN-Α/Β) HAVE BEENTRADITIONALLY ASSOCIATED WITH ANTIVIRALRESPONSES, THEIR IMPORTANCE IN HOST DEFENSEAGAINST BACTERIAL PATHOGENS IS BEINGINCREASINGLY APPRECIATED. LITTLE IS KNOWN,HOWEVER, ABOUT THE OCCURRENCE ANDFUNCTIONAL ROLE OF IFN-Α/Β PRODUCTION INRESPONSE TO PATHOGENIC YEASTS. HERE, WEFOUND THAT CONVENTIONAL DCS, BUT NOTMACROPHAGES NOR PLASMACYTOID DCS, MOUNTEDIFN-Β RESPONSES AFTER IN VITRO STIMULATIONWITH CANDIDA SPP. OR SACCHAROMYCESCEREVISIAE. THESE RESPONSES ABSOLUTELYREQUIRED MYD88, A TOLL-LIKE RECEPTOR (TLR)ADAPTOR MOLECULE, AND WERE PARTIALLYDEPENDENT ON TLR9 AND TLR7. MOREOVER,CANDIDA DNA, AS WELL AS RNA, COULDRECAPITULATE THE IFN-Β RESPONSE. AFTERINTRAVENOUS CHALLENGE WITH CANDIDA ALBICANS,MOST MICE LACKING THE IFN-Α/Β RECEPTOR DIEDFROM THEIR INABILITY TO CONTROL FUNGALGROWTH, WHEREAS ALL WT CONTROLS SURVIVED.THESE DATA SUGGEST THAT RECOGNITION OF YEASTNUCLEIC ACIDS BY TLR7 AND TLR9 TRIGGERS AHOST-PROTECTIVE IFN-Α/Β RESPONSE.


EUR J IMMUNOL. 2011 JUL;41(7):1969-79. DOI:10.1002/EJI.201141490.ANNO: 2011 - ISBN:

Titolo

A SURFACE PROTEIN OF STREPTOCOCCUS SUISSEROTYPE 2 IDENTIFIED BY PROTEOMICS PROTECTSMICE AGAINST INFECTION.

Autori

MANDANICI F, GÓMEZ-GASCÓN L, GARIBALDI M,OLAYA-ABRIL A, LUQUE I, TARRADAS C, MANCUSO G,PAPASERGI S, BÁRCENA JA, TETI G, BENINATI C,


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RODRÍGUEZ-ORTEGA MJ.

Abstract

STREPTOCOCCUS SUIS SEROTYPE 2 IS A MAJORGRAM-POSITIVE SWINE PATHOGEN, CAUSING ALSOZOONOSES. WE DESCRIBE HERE THEIMMUNOPROTECTIVE ACTIVITY IN AN IN VIVO ANIMALMODEL OF A SEROTYPE-2 CELL WALL PROTEIN,DESIGNATED SAT, WHICH WAS IDENTIFIED BY APREVIOUSLY VALIDATED PROTEOMICS APPROACHCONSISTING OF THE PROTEASE DIGESTION OF LIVEBACTERIA AND THE SELECTIVE RECOVERY OFEXPOSED DOMAINS, FOLLOWED BY LC/MS/MSANALYSIS. INCREASED SURVIVAL RATE (80%) ANDDECREASED BACTERIAL BURDEN WERE OBSERVEDIN MICE IMMUNIZED WITH A RECOMBINANT SATFRAGMENT, SUGGESTING THAT THIS PROTEIN IS APOTENTIAL VACCINE CANDIDATE AGAINSTSEROTYPE-2 INFECTION.


J PROTEOMICS. 2010 NOV 10;73(12):2365-9. EPUB 2010JUL 23ANNO: 2010 - ISBN:

Titolo

BACTERIAL RECOGNITION BY TLR7 IN THELYSOSOMES OF CONVETIONAL DENDRITIC CELLS.

Autori

MANCUSO G., GAMBUZZA M., MIDIRI A., BIONDOC.,PAPASERGI S., AKIRA S., TETI G., BENINATI C.

Abstract

LITTLE IS KNOWN OF HOW AND WHERE BACTERIALRECOGNITION TRIGGERS THE INDUCTION OF TYPE I


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INTERFERON. WHETHER THE TYPE OF RECOGNITIONRECEPTOR USED IN THESE RESPONSES ISDETERMINED BY THE SUBCELLULAR LOCATION OFBACTERIA IS NOT UNDERSTOOD. HERE WE SHOWTHAT PHAGOSOMAL BACTERIA SUCH AS GROUP BSTREPTOCOCCUS, BUT NOT CYTOSOLIC BACTERIA,POTENTLY INDUCED INTERFERON IN CONVENTIONALDENDRITIC CELLS BY A MECHANISM THAT REQUIREDTOLL-LIKE RECEPTOR 7, THE ADAPTOR MYD88 ANDTHE TRANSCRIPTION FACTOR IRF1, ALL OF WHICHLOCALIZED TOGETHER WITH BACTERIAL PRODUCTSIN DEGRADATIVE VACUOLES BEARING LYSOSOMALMARKERS. THUS, THIS CELL TYPE–SPECIFICRECOGNITION PATHWAY LINKS LYSOSOMALRECOGNITION OF BACTERIAL RNA WITH A ROBUST,HOST-PROTECTIVE INTERFERON RESPONSE.


NAT. IMMUNOL. 2009 JUN ; 10 (6):587-594.ANNO: 2009 - ISBN:

Titolo

TOLL-LIKE RECEPTOR 2 DEPENDENTIMMUNOGENICITY OF GLYCOCONJUGATE VACCINESCONTAINING CHEMICALLY DERIVED ZWITTERIONICPOLYSACCHARIDES

Autori

GALLORINI S., BERTI F., MANCUSO G., COZZI R.,TORTOLI M., VOLPINI G., TELFORD J.L., BENINATI C.,MAIONE D., WACK A.

Abstract

GROUP B STREPTOCOCCUS (GBS) CAUSES SERIOUSINFECTION IN NEONATES AND IS AN IMPORTANTTARGET OF VACCINE DEVELOPMENT. ZWITTERIONICPOLYSACCHARIDES (ZPS), OBTAINED THROUGHCHEMICAL INTRODUCTION OF POSITIVE CHARGESINTO ANIONIC POLYSACCHARIDES (PS) FROM GBS,


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HAVE THE ABILITY TO ACTIVATE HUMAN AND MOUSEANTIGEN PRESENTING CELLS (APCS) THROUGH TOLL-LIKE RECEPTOR 2 (TLR2). TO GENERATE APOLYSACCHARIDE VACCINE WITH ANTIGEN (AG) ANDADJUVANT PROPERTIES IN ONE MOLECULE, WE HAVECONJUGATED ZPS WITH A CARRIER PROTEIN. ZPS-GLYCOCONJUGATES INDUCE HIGHER T-CELL AND ABRESPONSES TO CARRIER AND PS, RESPECTIVELY,COMPARED TO CONTROL PS-GLYCOCONJUGATESMADE WITH THE NATIVE POLYSACCHARIDE FORM.THE INCREASED IMMUNOGENICITY OF ZPS-CONJUGATES CORRELATES WITH THEIR ABILITY TOACTIVATE DENDRITIC CELLS (DCS). MOREOVER,PROTECTION OF MOTHERS OR NEONATE OFFSPRINGFROMLETHAL GBS CHALLENGE IS BETTER WHENMOTHERS ARE IMMUNIZED WITH ZPS-CONJUGATESCOMPARED TO IMMUNIZATION WITH PS-CONJUGATES.IN TLR2 KNOCKOUT MICE, ZPS-CONJUGATES LOSEBOTH THEIR INCREASED IMMUNOGENICITY ANDPROTECTIVE EFFECT AFTER VACCINATION. WHENZPS ARE COADMINISTERED AS ADJUVANTS WITHUNCONJUGATED TETANUS TOXOID (TT), THEY HAVETHE ABILITY TO INCREASE THE TT-SPECIFICANTIBODY TITER. IN CONCLUSION,GLYCOCONJUGATES CONTAINING ZPS ARE POTENTVACCINES. THEY TARGET AG TO TLR2-EXPRESSINGAPCS AND ACTIVATE THESE APCS, LEADING TOBETTER T-CELL PRIMING AND ULTIMATELY TO HIGHERPROTECTIVE AB TITERS. THUS, RATIONAL CHEMICALDESIGN CAN GENERATE POTENT PS-ADJUVANTSWITH WIDE APPLICATION, INCLUDINGGLYCOCONJUGATES AND COADMINISTRATION WITHUNRELATED PROTEIN AGS.


PNAS 2009, VOL. 106, N°41, PP. 17481-17486ANNO: 2009 - ISBN:

Titolo

IMMUNOGENIC MIMICS OF BRUCELLALIPOPOLYSACCHARIDE EPITOPES.

Autori


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BENINATI C, GARIBALDI M, LO PASSO C, MANCUSO G,PAPASERGI S, GARUFI G, PERNICE I, TETI G, FELICI F.

Abstract

BRUCELLA MELITENSIS AND BRUCELLA ABORTUSARE RESPONSIBLE FOR BRUCELLOSIS IN BOVINEAND OVINE SPECIES AND FOR MALTA FEVER INHUMANS. THE LIPOPOLYSACCHARIDE (LPS) OFBRUCELLA IS AN IMPORTANT VIRULENCE FACTORAND CAN ELICIT PROTECTIVE ANTIBODIES. BECAUSEOF THEIR POTENTIAL IMPORTANCE IN VACCINEDESIGN AND IN SEROLOGICAL DIAGNOSIS, WEDEVELOPED PEPTIDES MIMICKING THE ANTIGENICPROPERTIES OF DISTINCTIVE ANTIGENICDETERMINANTS OF BRUCELLA LPS. THESE PEPTIDESWERE SELECTED FROM SEVERAL PHAGE DISPLAYRANDOM PEPTIDE LIBRARIES FOR THEIR ABILITY TOBIND MONOCLONAL ANTIBODIES DIRECTED AGAINSTTHE A- OR C-TYPE EPITOPES OF BRUCELLA LPS.PLASMIDS ENCODING FOR TWO OF THE ISOLATEDPEPTIDES INDUCED, AFTER DNA IMMUNIZATION, LPS-SPECIFIC ANTIBODY RESPONSES. ALTHOUGH THESERESPONSES WERE ONLY MODERATE IN EXTENT,THESE DATA FURTHER SUGGEST THE FEASIBILITY OFUSING PEPTIDE MIMICS OF CARBOHYDRATEEPITOPES AS IMMUNOGENS, A PROPERTY WHICHMAY BE USEFUL IN THE DESIGN OF NOVEL ANTI-BRUCELLA VACCINES.


PEPTIDES. 2009 OCT;30(10):1936-9. EPUB 2009 JUL 22ANNO: 2009 - ISBN:

Titolo

IFN-ALPHA/BETA SIGNALING IS REQUIRED FORPOLARIZATION OF CYTOKINE RESPONSES TOWARD APROTECTIVE TYPE I PATTERN DURINGEXPERIMENTAL CRYPTOCOCCOSIS.


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Autori

BIONDO C, MIDIRI A, GAMBUZZA M, GERACE E,FALDUTO M, GALBO R, BELLANTONI A, BENINATI C,TETI G., LEANDERSON T, MANCUSO G.

Abstract

THE ANTIVIRAL ACTIVITIES OF TYPE I IFNS HAVELONG BEEN ESTABLISHED. HOWEVER,COMPARATIVELY LITTLE IS KNOWN OF THEIR ROLE INDEFENSES AGAINST NONVIRAL PATHOGENS. WEEXAMINED HERE THE EFFECTS OF TYPE I IFNS ONHOST RESISTANCE AGAINST THE MODELPATHOGENIC YEAST CRYPTOCOCCUS NEOFORMANS.AFTER INTRATRACHEAL OR I.V. CHALLENGE WITHTHIS FUNGUS, MOST MICE LACKING EITHER THE IFN- /RECEPTOR (IFN- / R) OR IFN- DIED FROMUNRESTRAINED PNEUMONIA AND ENCEPHALITIS,WHILE ALL WILD-TYPE CONTROLS SURVIVED. THEPULMONARY IMMUNE RESPONSE OF IFN-A/BR -/- MICEWAS CHARACTERIZED BY INCREASED EXPRESSIONOF IL-4, IL-13, AND IL-10, DECREASED EXPRESSIONOF TNF-ALPHA, IFN-GAMMA, INDUCIBLE NOSYNTHETASE, AND CXCL10, AND SIMILAR LEVELS OFIL-12 MRNA, COMPARED WITH WILD-TYPE CONTROLS.HISTOPATHOLOGICAL ANALYSIS SHOWEDEOSINOPHILIC INFILTRATES IN THE LUNGS OF IFN-A/BR -/- MICE, ALTHOUGH THIS CHANGE WAS LESSEXTENSIVE THAN THAT OBSERVED IN SIMILARLYINFECTED IFN-GR-DEFICIENT ANIMALS. TYPE I IFNRESPONSES COULD NOT BE DETECTED IN THE LUNGAFTER INTRATRACHEAL CHALLENGE. HOWEVER,SMALL, BUT STATISTICALLY SIGNIFICANT,ELEVATIONS IN IFN-BETA LEVELS WERE MEASUREDIN THE SUPERNATANTS OF BONE MARROW-DERIVEDMACROPHAGES OR DENDRITIC CELLS INFECTEDWITH C. NEOFORMANS. OUR DATA DEMONSTRATETHAT TYPE I IFN SIGNALING IS REQUIRED FORPOLARIZATION OF CYTOKINE RESPONSES TOWARD APROTECTIVE TYPE I PATTERN DURINGCRYPTOCOCCAL INFECTION.



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J. IMMUNOL. 2008 VOL. 181 (1), PP. 566-573.ANNO: 2008 - ISBN:

Titolo

LIPOPROTEINS ARE CRITICAL TLR2 ACTIVATINGTOXINS IN GROUP B STREPTOCOCCAL SEPSIS.

Autori

HENNEKE P, DRAMSI S, MANCUSO G, CHRAIBI K,PELLEGRINI E, THEILACKER C, HUBNER J, SANTOS-SIERRA S, TETI G., GOLENBOCK DT, POVART C, TRIEU-CUOT P.

Abstract

GROUP B STREPTOCOCCUS (GBS) IS THE MOSTIMPORTANT CAUSE OF NEONATAL SEPSIS, WHICH ISMEDIATED IN PART BY TLR2. HOWEVER, GBSCOMPONENTS THAT POTENTLY INDUCE CYTOKINESVIA TLR2 ARE LARGELY UNKNOWN. WE FOUND THATGBS STRAINS OF THE SAME SEROTYPE DIFFER INRELEASED FACTORS THAT ACTIVATE TLR2. SEVERALLINES OF GENETIC AND BIOCHEMICAL EVIDENCEINDICATED THAT LIPOTEICHOIC ACID (LTA), THE MOSTWIDELY STUDIED TLR2 AGONIST IN GRAM-POSITIVEBACTERIA, WAS NOT ESSENTIAL FOR TLR2ACTIVATION. WE THUS EXAMINED THE ROLE OF GBSLIPOPROTEINS IN THIS PROCESS BY INACTIVATINGTWO GENES ESSENTIAL FOR BACTERIALLIPOPROTEIN (BLP) MATURATION: THEPROLIPOPROTEIN DIACYLGLYCERYL TRANSFERASEGENE (LGT) AND THE LIPOPROTEIN SIGNALPEPTIDASE GENE (LSP). WE FOUND THAT LGTMODIFICATION OF THE N-TERMINAL SEQUENCECALLED LIPOBOX WAS NOT CRITICAL FOR LSPCLEAVAGE OF BLPS. IN THE ABSENCE OF LGT ANDLSP, LIPOPROTEIN SIGNAL PEPTIDES WEREPROCESSED BY THE TYPE I SIGNAL PEPTIDASE.IMPORTANTLY, BOTH THE LGT AND THE LSP MUTANTWERE IMPAIRED IN TLR2 ACTIVATION. IN CONTRASTTO RELEASED FACTORS, FIXED LGT AND LSP GBSCELLS EXHIBITED NORMAL INFLAMMATORY ACTIVITY


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INDICATING THAT EXTRACELLULAR TOXINS AND CELLWALL COMPONENTS ACTIVATE PHAGOCYTESTHROUGH INDEPENDENT PATHWAYS. IN ADDITION,THE LGT MUTANT EXHIBITED INCREASED LETHALITYIN A MODEL OF NEONATAL GBS SEPSIS. NOTABLY, LTACOMPRISED LITTLE, IF ANY, INFLAMMATORY POTENCYWHEN EXTRACTED FROM LGT GBS. IN CONCLUSION,MATURE BLPS, AND NOT LTA, ARE THE MAJOR TLR2ACTIVATING FACTORS FROM GBS ANDSIGNIFICANTLY CONTRIBUTE TO GBS SEPSIS.


J. IMMUNOL. 2008 VOL. 180 (9), PP. 6149-6158.ANNO: 2008 - ISBN:

Titolo

PEPTIDE MIMICS OF THE GROUP B MENINGOCOCCALCAPSULE INDUCE BACTERICIDAL AND PROTECTIVEANTIBODIES AFTER IMMUNIZATION.

Autori

LO PASSO C, ROMEO A, PERNICE I, DONATO P, MIDIRIA, MANCUSO G, ARIGÒ M, BIONDO C, GALBO R,PAPASERGI S, FELICI F, TETI G, BENINATI C.

Abstract

NEISSERIA MENINGITIDIS SEROGROUP B (MENB) IS ALEADING CAUSE OF SEPSIS AND MENINGITIS INCHILDREN. NO VACCINE IS AVAILABLE FOR THEPREVENTION OF THESE INFECTIONS BECAUSE THEGROUP B CAPSULAR POLYSACCHARIDE (CP) (MENBCP) IS UNABLE TO STIMULATE AN IMMUNE RESPONSE,DUE TO ITS SIMILARITY WITH HUMAN POLYSIALICACID. BECAUSE THE MENB CP BEARS BOTH HUMANCROSS-REACTIVE AND NON-CROSS-REACTIVEDETERMINANTS, WE DEVELOPED IMMUNOGENICPEPTIDE MIMICS OF THE LATTER EPITOPES.PEPTIDES WERE SELECTED FROM PHAGE DISPLAYLIBRARIES FOR THEIR ABILITY TO BIND TO A


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PROTECTIVE ANTI-MENB CP MAB. ONE OF THESEPEPTIDES (DESIGNATED 9M) INDUCED MARKEDELEVATIONS IN SERUM BACTERICIDAL ACTIVITY, BUTNOT POLYSIALIC ACID CROSS-REACTING ABS, AFTERGENE PRIMING FOLLOWED BY CARRIER-CONJUGATEBOOSTING. MOREOVER, THE OCCURRENCE OFBACTEREMIA WAS PREVENTED IN INFANT RATS BYADMINISTRATION OF IMMUNE SERA BEFORE MENBCHALLENGE. 9MIS A PROMISING LEAD CANDIDATEFOR THE DEVELOPMENT OF AN EFFECTIVE ANDAFFORDABLE ANTI-MENB VACCINE.


J. IMMUNOL. 2007 APR 1;178(7):4417-23.ANNO: 2008 - ISBN:

Titolo

TYPE I IFN SIGNALING IS CRUCIAL FOR HOSTRESISTANCE AGAINST DIFFERENT SPECIES OFPATHOGENIC BACTERIA.

Autori

MANCUSO G, MIDIRI A, BIONDO C, BENINATI C, ZUMMOS, GALBO R, TOMASELLO F, GAMBUZZA M, MACRI G,RUGGERI A, LEANDERSON T, TETI G.

Abstract

IT IS KNOWN THAT HOST CELLS CAN PRODUCE TYPE IIFNS (IFN-AB) AFTER EXPOSURE TO CONSERVEDBACTERIAL PRODUCTS, BUT THE FUNCTIONALCONSEQUENCES OF SUCH RESPONSES ON THEOUTCOME OF BACTERIAL INFECTIONS AREINCOMPLETELY UNDERSTOOD. WE SHOW IN THISSTUDY THAT IFN-AB SIGNALING IS CRUCIAL FORHOST DEFENSES AGAINST DIFFERENT BACTERIA,INCLUDING GROUP B STREPTOCOCCI (GBS),PNEUMOCOCCI, AND ESCHERICHIA COLI. INRESPONSE TO GBS CHALLENGE, MOST MICELACKING EITHER THE IFN-ABR OR IFN-B DIED FROM


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UNRESTRAINED BACTEREMIA, WHEREAS ALL WILD-TYPE CONTROLS SURVIVED. THE EFFECT OF IFN-ABRDEFICIENCY WAS MARKED, WITH MORTALITYSURPASSING THAT SEEN IN IFN-GR-DEFICIENT MICE.ANIMALS LACKING BOTH IFN-ABR AND IFN-GRDISPLAYED ADDITIVE LETHALITY, SUGGESTING THATTHE TWO IFN TYPES HAVE COMPLEMENTARY ANDNONREDUNDANT ROLES IN HOST DEFENSES.INCREASED PRODUCTION OF IFN-AB WAS DETECTEDIN MACROPHAGES AFTER EXPOSURE TO GBS.MOREOVER, IN THE ABSENCE OF IFN-AB SIGNALING,A MARKED REDUCTION IN MACROPHAGEPRODUCTION OF IFN-GAMMA, NO, AND TNF-ALPHAWAS OBSERVED AFTER STIMULATION WITH LIVEBACTERIA OR WITH PURIFIED LPS. COLLECTIVELY,OUR DATA DOCUMENT A NOVEL, FUNDAMENTALFUNCTION OF IFN-AB IN BOOSTING MACROPHAGERESPONSES AND HOST RESISTANCE AGAINSTBACTERIAL PATHOGENS. THESE DATA MAY BEUSEFUL TO DEVISE ALTERNATIVE STRATEGIES TOTREAT BACTERIAL INFECTIONS.


J. IMMUNOL. 2007 MAR 1;178(5):3126-33.ANNO: 2007 - ISBN:

Titolo

TRANSCRIPTIONAL REGULATION OF IL-8 BYSTAPHYLOCOCCUS AUREUS IN HUMANCONJUNCTIVAL CELLS INVOLVES ACTIVATION OFAP-1.

Autori

VENZA I, CUCINOTTA M, CARISTI S, MANCUSO G, TETID.

Abstract

TO IDENTIFY SIGNAL TRANSDUCTION PATHWAYSINVOLVED IN INTERLEUKIN (IL)-8 EXPRESSION BY


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HUMAN CONJUNCTIVAL CELLS CHALLENGED WITHSTAPHYLOCOCCUS AUREUS. METHODS:CONJUNCTIVAL CELLS WERE CULTURED IN THEPRESENCE OF LIVE OR HEAT-KILLED S. AUREUS. IL-8PROTEIN AND MRNA WERE DETERMINED BY ELISAAND RT-PCR, RESPECTIVELY. ACTIVATION OFMITOGEN-ACTIVATED PROTEIN KINASES (MAPKS) ANDNF-KAPPAB WAS ANALYZED BY WESTERN BLOTANALYSIS WITH PHOSPHOSPECIFIC ANTIBODIES.CONJUNCTIVAL CELLS WERE TRANSFECTED WITHWILD-TYPE (WT) OR MUTATED IL-8 PROMOTERS(IL-8-97, LACKING THE AP-1 SITE; IL-8-97 MUTANTC/EBP; IL-8-97 MUTANT NF-KAPPAB; IL-8/AP-1 DOUBLEMUTANT FOR C/EBP AND NF-KAPPAB) OR C-JUN-NH(2)-TERMINAL KINASE (JNK)-RESPONSIVE GAL-C-JUN. INFURTHER EXPERIMENTS, CELLS WERECOTRANSFECTED WITH WT IL-8 PROMOTER ANDEXPRESSION PLASMIDS FOR P38MAPK-RESPONSIVEC/EBP HOMOLOGOUS PROTEIN (CHOP) OR WT ORDOMINANT NEGATIVE TRANSACTIVATION DOMAINMUTANT (TAM-67) C-JUN. A PROTEIN-DNA BINDINGSTUDY WAS PERFORMED BY ELECTROPHORETICMOBILITY SHIFT ASSAY (EMSA), TO IDENTIFY THETRANSCRIPTION FACTORS BOUND TO THE IL-8PROMOTER. RESULTS: S. AUREUS INDUCEDSIGNIFICANT IL-8 EXPRESSION AND SYNTHESIS INHUMAN CONJUNCTIVAL EPITHELIAL CELLS BYACTIVATING C-JUN PHOSPHORYLATION ANDTRANSACTIVATION POTENTIAL VIA JNK. THE IL-8PROMOTER ACTIVATION WAS NF-KAPPAB- ANDP38MAPK-INDEPENDENT. TRANSFECTION AND EMSAEXPERIMENTS SUGGESTED THAT ONLY AP-1TRANSCRIPTION FACTORS WERE NECESSARY FOROPTIMAL IL-8 EXPRESSION. CONCLUSIONS: HUMANCONJUNCTIVAL EPITHELIAL CELLS POSSESS THEABILITY TO RESPOND TO GRAM-POSITIVE S. AUREUSAND TO ACTIVATE THE INNATE IMMUNE RESPONSE BYTHE IL-8 GENE EXPRESSION. THESE RESULTS ARETHE FIRST TO DELINEATE THE TRANSCRIPTIONFACTORS INVOLVED IN S. AUREUS-INDUCED IL-8RELEASE BY CONJUNCTIVAL EPITHELIUM.


INVEST OPHTHALMOL VIS SCI. 2007 JAN;48(1):270-6.ANNO: 2007 - ISBN:


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Titolo

PEPTIDE MIMICS OF THE GROUP B MENINGOCOCCALCAPSULE INDUCE BACTERICIDAL AND PROTECTIVEANTIBODIES AFTER IMMUNIZATION

Autori

LO PASSO, CARLA ROMEO, ANGELA PERNICE, IDAMIDIRI, ANGELINA MANCUSO, GIUSEPPE BIONDO,CARMELO GALBO, ROBERTA PAPASERGI, SALVATOREFELICI, FRANCO TETI, GIUSEPPE

Abstract

NEISSERIA MENINGIDDIS SEROGROUP, B (MENB) IS ALEADING CAUSE OF SEPSIS AND MENINGITIS INCHILDREN. NO VACCINE IS AVAILABLE FOR THEPREVENTION OF THESE INFECTIONS BECAUSE THEGROUP B CAPSULAR POLYSACCHARIDE (CP) (MENB;CP) IS UNABLE TO STIMULATE AN IMMUNE RESPONSE,DUE TO ITS SIMILARITY WITH HUMAN POLYSIALICACID. BECAUSE THE MENB; CP BEARS BOTH HUMANCROSS-REACTIVE AND NON-CROSS-REACTIVEDETERMINANTS, WE DEVELOPED IMMUNOGENICPEPTIDE MIMICS OF THE LATTER EPITOPES.PEPTIDES WERE SELECTED FROM PHAGE DISPLAYLIBRARIES FOR THEIR ABILITY TO BIND TO APROTECTIVE ANTI-MENB CP MAB. ONE OF THESEPEPTIDES (DESIGNATED 9M) INDUCED MARKEDELEVATIONS IN SERUM BACTERICIDAL ACTIVITY, BUTNOT POLYSIALIC ACID CROSS-REACTING ABS, AFTERGENE PRIMING FOLLOWED BY CARRIER-CONJUGATEBOOSTING. MOREOVER, THE OCCURRENCE OFBACTEREMIA WAS PREVENTED IN INFANT RATS BYADMINISTRATION OF INUMME SERA BEFORE MENBCHALLENGE. 9M IS A PROMISING LEAD CANDIDATEFOR THE DEVELOPMENT OF AN EFFECTIVE ANDAFFORDABLE ANTI-MENB VACCINE.



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J IMMUNOL. 2007 APR 1;178(7):4417-23ANNO: 2007 - ISBN:

Titolo

ANTIIDIOTYPIC DNA VACCINATION INDUCES SERUMBACTERICIDAL ACTIVITY AND PROTECTION AGAINSTGROUP B MENINGOCOCCI.

Autori

BENINATI C, MIDIRI A, MANCUSO G, BIONDO C, ARIGOM, GERACE E, PAPASERGI S, GAMBUZZA M, BORETTIM, MAGLIANI W, CONTI S, POLONELLI L, TETI G.

Abstract

NO VACCINE IS AVAILABLE FOR PREVENTINGINFECTIONS BY SEROGROUP B NEISSERIAMENINGITIDIS (MENB), WHICH ACCOUNTS FOR AMAJOR PORTION OF MENINGOCOCCAL CASES INDEVELOPED COUNTRIES, BECAUSE OF THE POORIMMUNOGENICITY OF THE CAPSULARPOLYSACCHARIDE (CP) EVEN AFTER PROTEINCONJUGATION. WE HAVE PREVIOUSLY INDUCEDANTICAPSULAR ANTIBODIES BY IMMUNIZATION WITHA SINGLE CHAIN VARIABLE FRAGMENT (SCFV), WHICHMIMICS A PROTECTIVE CP EPITOPE. THISSURROGATE ANTIGEN, HOWEVER, WAS INEFFECTIVEAT INDUCING SERUM BACTERICIDAL ACTIVITY, ANACCEPTED MARKER OF PROTECTION IN HUMANS.SERUM BACTERICIDAL ACTIVITY WAS CONSISTENTLYACHIEVED BY IMMUNIZING MICE WITH THE SCFV-ENCODING GENE. IMMUNIZATION WITH VECTORSWITHOUT A SECRETORY SIGNAL SEQUENCE BEFORETHE SCFV RESULTED IN MARKEDLY HIGHERBACTERICIDAL ACTIVITY RELATIVE TO THOSE WITHSUCH A SEQUENCE. THE INDUCED ANTIBODIES WERECAPSULE SPECIFI C, AS SHOWN BY COMPLETEINHIBITION OF BACTERICIDAL ACTIVITY BY PURIFI EDMENB CP AND BY RESISTANCE TO KILLING OF MENAOR MENC. MOREOVER, THESE ANTIBODIES WEREPREDOMINANTLY OF THE IGG2A ISOTYPE, REFLECTING A T HELPER TYPE 1 RESPONSE.


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ADMINISTRATION OF SERA FROM SCFV GENE–VACCINATED ANIMALS PROTECTED INFANT RATSAGAINST MENB BACTEREMIA. THESE DATAILLUSTRATE THE POTENTIAL OF VACCINATION WITHGENES ENCODING CAPSULAR MIMICS IN PROVIDINGPROTECTION AGAINST MENB AND OTHERENCAPSULATED BACTERIA.


J EXP MED. 2006 JAN 23; 203(1):111-8.ANNO: 2006 - ISBN:

Titolo

COMPARISON OF LIPOTEICHOIC ACID FROMDIFFERENT SEROTYPES OF STREPTOCOCCUSPNEUMONIAE.

Autori

DRAING C, PFITZENMAIER M, ZUMMO S, MANCUSO G,GEYER A, HARTUNG T, VON AULOCK S.

Abstract

PNEUMOCOCCAL LIPOTEICHOIC ACID (LTA) IS KNOWNTO HAVE A COMPLETELY DIFFERENT CHEMICALSTRUCTURE COMPARED WITH THAT OFSTAPHYLOCOCCUS AUREUS: THEPOLYGLYCEROPHOSPHATE IN THE BACKBONE ISREPLACED IN THE PNEUMOCOCCAL LTA BY APENTAMER REPEATING UNIT CONSISTING OF ONERIBITOL AND A TETRASACCHARIDE CARRYING THEUNUSUAL SUBSTITUENTS PHOSPHOCHOLINE ANDN-ACETYL-D-GALACTOSAMINE. NEITHER D-ALANINENOR N-ACETYL-D-GLUCOSAMINE, WHICH PLAYCENTRAL ROLES IN THE BIOLOGICAL ACTIVITY OFTHE STAPHYLOCOCCAL LTA, HAS BEEN REPORTED.THE EXTRACTION USING BUTANOL IS MORE GENTLECOMPARED WITH THE PREVIOUSLY REPORTEDCHLOROFORM-METHANOL EXTRACTION ANDRESULTS IN A HIGHER YIELD OF LTA. WE


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CHARACTERIZED THE LTA OF TWO DIFFERENTSTRAINS OF STREPTOCOCCUS PNEUMONIAE:R6(SEROTYPE 2) AND FP23 (SEROTYPE 4). NMRANALYSIS CONFIRMED THE STRUCTURE OF LTA FROMR6 BUT SHOWED THAT ITS RIBITOL CARRIES ANN-ACETYL-D-GALACTOSAMINE SUBSTITUENT. THENMR DATA FOR THE LTA FROM FP23 INDICATE THATTHIS LTA ADDITIONALLY CONTAINS RIBITOLBOUNDD-ALANINE. DOSE-RESPONSE CURVES OF THE TWOPNEUMOCOCCAL LTAS IN HUMAN WHOLE BLOODREVEALED THAT LTA FROM FP23 WAS SIGNIFICANTLYMORE POTENT THAN LTA FROM R6 WITH REGARD TOTHE INDUCTION OF ALL CYTOKINES MEASURED(TUMOR NECROSIS FACTOR, INTERLEUKIN-1 (IL-1),IL-8, IL-10, GRANULOCYTE COLONY-STIMULATINGFACTOR, AND INTERFERON GAMMA). HOWEVER,OTHER CHARACTERISTICS, SUCH AS LACK OFINHIBITION BY ENDOTOXIN-SPECIFIC LAL-F, TOLL-LIKE RECEPTOR 2 AND NOT 4 DEPENDENCE, ANDLACK OF STIMULATION OF NEUTROPHILICGRANULOCYTES, WERE SHARED BY BOTH LTAS. THISIS THE FIRST REPORT OF A DIFFERENCE IN THESTRUCTURE OF LTABETWEEN TWO PNEUMOCOCCALSEROTYPES RESULTING IN DIFFERENTIMMUNOSTIMULATORY POTENCIES.


J. BIOL. CHEM. 2006 NOV 10;281(45):33849-59.ANNO: 2006 - ISBN:

Titolo

C-JUN KINASE IS A CRITICAL SIGNALING MOLECULEIN A NEONATAL MODEL OF GROUP BSTREPTOCOCCAL SEPSIS.

Autori

KENZEL S, MANCUSO G, MALLEY R, TETI G,GOLENBOCK DT, HENNEKE P. J

Abstract


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GROUP B STREPTOCOCCUS (GBS) IS THE MAJORCAUSE OF SEPSIS IN NEWBORN INFANTS. IN VITRO,INACTIVATED GBS STIMULATES MACROPHAGES TOPRODUCE INFLAMMATORY PROTEINS VIA THE TLRADAPTER PROTEIN MYD88. FURTHERMORE,INFLAMMATORY CYTOKINE RELEASE IN RESPONSETO GBS GREATLY EXCEEDS THAT FOLLOWINGSTIMULATION WITH PNEUMOCOCCI. IN THIS STUDY,WE ATTEMPTED TO UNRAVEL SIGNALING EVENTSTHAT ARE INVOLVED IN GBS-, BUT NOTSTREPTOCOCCUS PNEUMONIAE-STIMULATEDPHAGOCYTES TO IDENTIFY MOLECULAR TARGETSFOR ADJUNCTIVE SEPSIS THERAPY. WE FOUND THATINACTIVATED GBS AND S. PNEUMONIAE DIFFERED INTHE ACTIVATION OF THE MAPK JNK, BUT NOT I BKINASE. FURTHERMORE, JNK WAS ESSENTIAL FORTHE TRANSCRIPTIONAL ACTIVATION OFINFLAMMATORY CYTOKINE GENES IN RESPONSE TOGBS. INHIBITION OF JNK BY THEANTHRAPYRAZOLONE SP600125 ABROGATED GBS-INDUCED CYTOKINE FORMATION VIA AN AP-1- AND NF-B-DEPENDENT MECHANISM WITHOUT IMPAIRINGANTIBACTERIAL PROPERTIES SUCH ASPHAGOCYTOSIS OF GBS AND THE FORMATION OFINTRACELLULAR OXIDATIVE SPECIES. IN CONTRAST,INHIBITION OF THE MAPK P38 IMPAIRED BOTHANTIBACTERIAL PROCESSES. IN A NEONATAL MOUSEMODEL OF GBS SEPSIS SP600125 INHIBITED THEINFLAMMATORY RESPONSE AND IMPROVEDSURVIVAL. IN CONCLUSION, JNK PLAYS A MAJORROLE IN THE INFLAMMATORY, BUT NOT IN THE DIRECTANTIBACTERIAL RESPONSE TO INACTIVATED GBS,AND MAY THUS SERVE AS A RATIONAL TARGET FORAN ADJUNCTIVE GBS SEPSIS THERAPY.


IMMUNOL. 2006 MAR 1;176(5):3181-8.ANNO: 2006 - ISBN:

Titolo

IDENTIFICATION OF MAJOR PROTEINS SECRETED BYCRYPTOCOCCUS NEOFORMANS.


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Autori

BIONDO C, MANCUSO G, MIDIRI A, BOMBACI M,MESSINA L, BENINATI C, TETI G.

Abstract

THE CHARACTERIZATION OF PROTEINS SECRETEDBY CRYPTOCOCCUS NEOFORMANS IS OF RELEVANCETO THE IDENTIFICATION OF VACCINE CANDIDATES,BECAUSE CONCENTRATED SUPERNATANTS FROMTHE FUNGUS HAVE BEEN SHOWN TO BEIMMUNOPROTECTIVE IN PREVIOUS STUDIES. AFTERFRACTIONATION OF SUPERNATANTS BY ANIONEXCHANGE CHROMATOGRAPHY AND PREPARATIVEELECTROPHORESIS, WE OBTAINED THE N-TERMINALAMINO ACID SEQUENCES OF 13 MAJOR PROTEINS.USING A C. NEOFORMANS NUCLEOTIDE DATABASE,WE WERE ABLE TO CLONE AND SEQUENCE THEORFS CODING FOR 12 OF THESE PROTEINS. SOMEOF THE GENES ARE IDENTICAL TO PREVIOUSLYDESCRIBED ONES, WHILE SIX ENCODE NOVELPROTEINS, INCLUDING FOUR PUTATIVEMANNOPROTEINS. THE MOLECULARCHARACTERIZATION OF THESE AND OTHERSECRETED PRODUCTS MAY PROVIDE USEFULINFORMATION IN THE DEVELOPMENT OFIMMUNEBASED STRATEGIES TO CONTROLCRYPTOCOCCOSIS.


FEMS YEAST RES. 2006 JUN; 6 (4):645-51.ANNO: 2006 - ISBN:

Titolo

IDENTIFICATION OF A UNIVERSAL GROUP BSTREPTOCOCCUS VACCINE BY MULTIPLE GENOMESCREEN.

Autori


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D. MAIONE, I. MARGARIT, C. D. RINAUDO, V.MASIGNANI, M. MORA, M. SCARSELLI, H. TETTELIN, C.BRETTONI, E. T. IACOBINI, R. ROSINI, N. D'AGOSTINO,L. MIORIN, S. BUCCATO, M. MARIANI, G. GALLI, R.NOGAROTTO, V. N. DEI, F. VEGNI, C. FRASER, G.MANCUSO, G.

Abstract

GROUP B STREPTOCOCCUS (GBS) IS AMULTISEROTYPE BACTERIAL PATHOGENREPRESENTING A MAJOR CAUSE OF LIFE-THREATENING INFECTIONS IN NEWBORNS. TODEVELOP A BROADLY PROTECTIVE VACCINE, WEANALYZED THE GENOME SEQUENCES OF EIGHT GBSISOLATES AND CLONED AND TESTED 312 SURFACEPROTEINS AS VACCINES. FOUR PROTEINS ELICITEDPROTECTION IN MICE, AND THEIR COMBINATIONPROVED HIGHLY PROTECTIVE AGAINST A LARGEPANEL OF STRAINS, INCLUDING ALL CIRCULATINGSEROTYPES. PROTECTION ALSO CORRELATED WITHANTIGEN ACCESSIBILITY ON THE BACTERIALSURFACE AND WITH THE INDUCTION OFOPSONOPHAGOCYTIC ANTIBODIES. MULTIGENOMEANALYSIS AND SCREENING DESCRIBED HEREREPRESENT A POWERFUL STRATEGY FORIDENTIFYING POTENTIAL VACCINE CANDIDATESAGAINST HIGHLY VARIABLE PATHOGENS.


SCIENCE. 2005. VOL. 309, PP. 148-150.ANNO: 2005 - ISBN:

Titolo

CHARACTERIZATION OF TWO NOVELCRYPTOCOCCAL MANNOPROTEINS RECOGNIZED BYIMMUNE SERA.

Autori


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BIONDO C, MESSINA L, BOMBACI M, MANCUSO G,MIDIRI A, BENINATI C, CUSUMANO V, GERACE E,PAPASERGI S, TETI G.

Abstract

HOST DEFENSES AGAINST THE ENCAPSULATEDYEAST CRYPTOCOCCUS NEOFORMANS INVOLVEBOTH HUMORAL AND CELLMEDIATED IMMUNITY.MANNOPROTEINS (MPS) ARE A HETEROGENEOUSCLASS OF IMMUNODOMINANT GLYCOPROTEINSWHICH HAVE BEEN ONLY INCOMPLETELYCHARACTERIZED. IN THIS STUDY, WE REPORT ONTHE MOLECULAR FEATURES OF TWO NOVEL MPSTHAT ARE RECOGNIZED BY SERUM ANTIBODIESDURING CRYPTOCOCCOSIS. AFTER FRACTIONATIONOF EXTRACELLULAR CRYPTOCOCCAL PRODUCTS,MPS REACTED MORE STRONGLY THAN OTHERCOMPONENTS WITH SERA FROM C. NEOFORMANS-INFECTED AIDS PATIENTS. FURTHER FRACTIONATIONAND WESTERN BLOT ANALYSIS OF MPS EVIDENCEDTHE PRESENCE OF HIGHLY REACTIVE BANDS WITHMOLECULAR MASSES OF 250, 125, 115, AND 84 KDA.THE 115- AND 84-KDA BANDS CONTAINEDSIGNIFICANT AMOUNTS OF N-LINKEDOLIGOSACCHARIDES, AS SHOWN BY DECREASEDMOLECULAR MASS AFTER PEPTIDE-N-GLYCOSIDASEF TREATMENT. N-TERMINAL AMINO ACID SEQUENCESOF THE TWO BANDS WERE USED TO SEARCH C.NEOFORMANS NUCLEOTIDE DATABASES.HOMOLOGOUS GENOMIC SEQUENCES WERE USEDTO SYNTHESIZE DNA PROBES AND ISOLATE CDNACLONES CONTAINING THE FULL-LENGTH GENES,WHICH WERE DESIGNATED MP84 AND MP115. BOTHGENES SHOWED THE PRESENCE OF ASERINE/THREONINE-RICH REGION, A POTENTIAL SITEFOR HEAVY GLYCOSYLATION. MP84 AND MP115SHOWED HOMOLOGY WITH, RESPECTIVELY,POLYSACCHARIDE DEACETYLASES ANDCARBOXYLESTERASES FROM OTHER ORGANISMS.RECOMBINANT, DEGLYCOSYLATED PROTEINSEXPRESSED IN ESCHERICHIA COLI STILL REACTEDWITH SERA FROM PATIENTS, ALBEIT MORE WEAKLYTHAN NATURAL MPS, INDICATING THAT AT LEASTSOME OF THE REACTIVE EPITOPES WERE RETAINEDIN THE RECOMBINANT FORMS. IN CONCLUSION, WEIDENTIFIED TWO NOVEL MPS THAT ARE IMPORTANT


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TARGETS OF ANTIBODY RESPONSES DURINGCRYPTOCOCCOSIS. THESE DATA MAY BE USEFUL TODEVISE ALTERNATIVE IMMUNITY-BASED STRATEGIESTO CONTROL THE DISEASE.


INFECT IMMUN. 2005 NOV; 73 (11):7348-55.ANNO: 2005 - ISBN:

Titolo

MYD88 AND TLR2, BUT NOT TLR4, ARE REQUIRED FORHOST DEFENSE AGAINST CRYPTOCOCCUSNEOFORMANS.

Autori

BIONDO C, MIDIRI A, MESSINA L, TOMASELLO F,GARUFI G, CATANIA MR, BOMBACI M, BENINATI C, TETIG, MANCUSO G.

Abstract

WE INVESTIGATED HERE THE POTENTIAL ROLE OFTOLL-LIKE RECEPTORS (TLR) AND THE ADAPTORPROTEIN MYD88 IN INNATE IMMUNITY RESPONSES TOCRYPTOCOCCUS NEOFORMANS, A PATHOGENICENCAPSULATED YEAST. PERITONEAL MACROPHAGESFROM MYD88 –/– OR TLR2–/– MICE RELEASEDSIGNIFICANTLY LESS TNF-A, COMPARED WITH WILD-TYPE CONTROLS, AFTER IN VITRO STIMULATIONWITH WHOLE YEASTS. IN CONTRAST, NODIFFERENCES IN TNF-A RELEASE WERE NOTEDBETWEEN MACROPHAGES FROM C3H/HEJ MICE,WHICH HAVE A LOSS OF FUNCTION MUTATION INTLR4, RELATIVE TO C3H/HEN CONTROLS. WHENMYD88- OR TLR2-DEFICIENT MICE WERE INFECTEDWITH LOW DOSES OF THE H99 SEROTYPE A STRAIN,ALL OF THE CONTROL ANIMALS, BUT NONE OF MYD88–/– AND ONLY 38%OF THE TLR2 –/– ANIMALSSURVIVED, IN ASSOCIATION WITH HIGHER FUNGALBURDEN IN THE MUTANT MICE. BOTH MYD88 –/– AND


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TLR2–/– ANIMALS SHOWED DECREASED TNF-A,IL12P40 AND/OR IFN-C EXPRESSION IN VARIOUSORGANS DURING INFECTION. NO DIFFERENCE INSUSCEPTIBILITY TO EXPERIMENTALCRYPTOCOCCOSIS WAS FOUND BETWEEN C3H/HEJMICE AND C3H/HEN CONTROLS. IN CONCLUSION, OURDATA INDICATE THAT TLR2 AND MYD88, BUT NOTTLR4, CRITICALLY CONTRIBUTE TO ANTI-CRYPTOCOCCAL DEFENSES THROUGH THEINDUCTION OF INCREASED TNF-A, IL-12 AND IFN-CEXPRESSION.


EUR J IMMUNOL. 2005 MAR;35(3):870-8ANNO: 2005 - ISBN:

Titolo

BACTEROIDES FRAGILIS-DERIVEDLIPOPOLYSACCHARIDE PRODUCES CELL ACTIVATIONAND LETHAL TOXICITY VIA TLR4.

Autori

MANCUSO G., MIDIRI A., BIONDO C., BENINATI C.,GAMBUZZA M., MACRÌ D., BELLANTONI A., WEINTRAUBA., ESPEVIK T., AND G. TETI.

Abstract

BACTEROIDES FRAGILIS, WHICH IS PART OF THENORMAL INTESTINAL FLORA, IS A FREQUENT CAUSEOF SERIOUS DISEASE, ESPECIALLY IN DIABETIC ANDSURGICAL PATIENTS. IN THESE CONDITIONS, B.FRAGILIS LIPOPOLYSACCHARIDE (LPS) IS LIKELY TOPLAY A MAJOR PATHOPHYSIOLOGIC ROLE. B.FRAGILIS LPS IS STRUCTURALLY DIFFERENT FROMCLASSICAL ENTEROBACTERIAL LPS, WHOSEBIOLOGICAL ACTIVITIES ARE MEDIATED BY TOLL-LIKE RECEPTOR 4 (TLR4) ACTIVATION. THE ABILITYOF B. FRAGILIS LPS TO ACTIVATE TLR4 AND TLR2WAS INVESTIGATED HERE, SINCE EVIDENCE ON THIS


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ISSUE IS SCARCE AND CONTROVERSIAL. EACH OFFOUR DIFFERENT PROTEIN-FREE B. FRAGILIS LPSPREPARATIONS COULD INDUCE INTERLEUKIN-8RESPONSES IN CELLS COTRANSFECTED WITHTLR4/CD14/MD2 BUT NOT TLR4/CD14 ALONE. TWO OFTHE PREPARATIONS ALSO INDUCED CYTOKINEPRODUCTION IN CELLS COTRANSFECTED WITHTLR2/CD14 OR IN PERITONEAL MACROPHAGES FROMTLR4 MUTANT C3H/HEJ MICE. BOTH OF THESEACTIVITIES, HOWEVER, WERE LOST AFTERREPURIFICATION WITH A MODIFIED PHENOLREEXTRACTION PROCEDURE. IMPORTANTLY, ALLPREPARATIONS COULD INDUCE ENDOTOXIC SHOCKIN TLR2-DEFICIENT MICE, BUT NOT IN TLR4 MUTANTC3H/HEJ MICE. CONSISTENT WITH THESE FINDINGS,ANTI-TLR4 AND ANTI-CD14, BUT NOT ANTI-TLR2,ANTIBODIES COULD INHIBIT B. FRAGILIS LPS-INDUCED CYTOKINE PRODUCTION IN HUMANMONOCYTES. COLLECTIVELY, THESE RESULTSINDICATE THAT B. FRAGILIS LPS SIGNALS VIA ATLR4/CD14/MD2-DEPENDENT PATHWAY, AND IT ISUNABLE TO ACTIVATE TLR2. MOREOVER, OUR DATADOCUMENT THE OCCURRENCE OF TLR2-ACTIVATINGCONTAMINANTS EVEN IN HIGHLY PURIFIED B.FRAGILIS LPS PREPARATIONS. THIS MAY EXPLAINEARLIER CONTRADICTORY FINDINGS ON THE ABILITYOF B. FRAGILIS LPS TO ACTIVATE CELLS IN THEABSENCE OF FUNCTIONAL TLR4. THESE DATA MAY BEUSEFUL TO DEVISE STRATEGIES TO PREVENT THEPATHOPHYSIOLOGIC CHANGES OBSERVED DURING B.FRAGILIS SEPSIS AND TO BETTER UNDERSTANDSTRUCTURE-ACTIVITY RELATIONSHIPS OF LPS.


INFECT. IMMUN. 2005. 73:5620-5627ANNO: 2005 - ISBN:

Titolo

PROTECTIVE IMMUNIZATION AGAINST GROUP BMENINGOCOCCI USING ANTI-IDIOTYPIC MIMICS OFTHE CAPSULAR POLYSACCHARIDE.

Autori


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C. BENINATI, S. ARSENI, G. MANCUSO, W. MAGLIANI, S.CONTI, A. MIDIRI, C. BIONDO, L. POLONELLI AND G.TETI.

Abstract

USE OF THE SEROGROUP B MENINGOCOCCALCAPSULAR POLYSACCHARIDE (MENB CP) AS AVACCINE IS HAMPERED BY THE PRESENCE OFEPITOPES THAT CROSS-REACT WITH HUMANPOLYSIALIC ACID. AS NON-CROSS-REACTIVE,PROTECTIVE CAPSULAR EPITOPES HAVE ALSO BEENDESCRIBED, WE SET OUT TO DEVELOP PROTEINMIMICS OF ONE OF SUCH EPITOPES USING AS ATEMPLATE A HIGHLY PROTECTIVE MAB (MAB SEAM 3)RAISED AGAINST A CHEMICALLY MODIFIED FORM OFTHE MENB CP (N-PR MENB CP). USING PHAGEDISPLAY, ANTI-IDIOTYPIC SINGLE-CHAIN ABFRAGMENTS (SCFVS) WERE OBTAINED FROM SPLEENCELLS OF MICE IMMUNIZED WITH THE SEAM 3 MAB.TWO SEAM 3-SPECIFIC SCFVS COMPETED WITH N-PRMENB CP FOR BINDING TO EITHER MAB SEAM 3 ORRABBIT ABS PRESENT IN TYPING SERA. MOREOVER,IN MICE AND RABBITS THE SCFVS ELICITED THEPRODUCTION OF ABS REACTING WITH BOTH N-PRMENB CP AND WHOLE MENINGOCOCCI, BUT NOTWITH HUMAN POLYSIALIC ACID. THESE SCFV-INDUCED AB RESPONSES WERE BOOSTABLE AND OFTHE TH1 TYPE, AS SHOWN BY A PREDOMINANCE OFIGG2A. IN ADDITION, PASSIVE IMMUNIZATION WITHSERA FROM SCFV-IMMUNIZED ANIMALS PARTIALLYPROTECTED NEONATAL MICE FROM EXPERIMENTALINFECTION WITH GROUP B MENINGOCOCCI. INCONCLUSION, WE HAVE PRODUCED ANTI-IDIOTYPICSCFVS THAT MIMIC A PROTECTIVE MENB CP EPITOPEAND MAY BE USEFUL IN THE DEVELOPMENT OF ANALTERNATIVE GROUP B MENINGOCOCCAL VACCINE.


JOURNAL OF IMMUNOLOGY. 2004. 172:2461-2468.ANNO: 2004 - ISBN:

Titolo


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DUAL ROLE OF TLR2 AND MYELOID DIFFERENTIATIONFACTOR 88 IN A MOUSE MODEL OF INVASIVE GROUPB STREPTOCOCCAL DISEASE.

Autori

G. MANCUSO, A. MIDIRI, C. BENINATI, C. BIONDO, R.GALBO, S. AKIRA, P. HENNEKE, D. GOLENBOCK, AND G.TETI.

Abstract

TOLL-LIKE RECEPTORS (TLRS) ARE INVOLVED INPATHOGEN RECOGNITION BY THE INNATE IMMUNESYSTEM. DIFFERENT TLRS AND THE ADAPTORMOLECULE MYELOID DIFFERENTIATION FACTOR 88(MYD88) WERE PREVIOUSLY SHOWN TO MEDIATE INVITRO CELL ACTIVATION INDUCED BY GROUP BSTREPTOCOCCUS (GBS). THE PRESENT STUDYEXAMINED THE POTENTIAL IN VIVO ROLES OF TLR2AND MYD88 DURING INFECTION WITH GBS. WHENPUPS WERE INFECTED LOCALLY WITH A LOWBACTERIAL DOSE, NONE OF THE TLR2- OR MYD88-DEFICIENT MICE, BUT ALL OF THE WILD-TYPE ONES,WERE ABLE TO PREVENT SYSTEMIC SPREAD OF GBSFROM THE INITIAL FOCUS. BACTERIAL BURDEN WASHIGHER IN MYD88- THAN IN TLR2-DEFICIENT MICE,INDICATING A MORE PROFOUND DEFECT OF HOSTDEFENSE IN THE FORMER ANIMALS. IN CONTRAST, AHIGH BACTERIAL DOSE INDUCED HIGH LEVELBACTEREMIA IN BOTH MUTANT AND WILD-TYPE MICE.UNDER THESE CONDITIONS, HOWEVER, TLR2 ORMYD88 DEFICIENCY SIGNIFICANTLY PROTECTEDMICE FROM LETHALITY, CONCOMITANTLY WITHDECREASED CIRCULATING LEVELS OF TNF-ALPHAAND IL-6. ADMINISTRATION OF ANTI-TNF-ALPHA ABSTO WILD-TYPE MICE COULD MIMIC THE EFFECTS OFTLR2 OR MYD88 DEFICIENCY AND WAS DETRIMENTALIN THE LOW DOSE MODEL, BUT PROTECTIVE IN THEHIGH DOSE MODEL. IN CONCLUSION, THESE DATAHIGHLIGHT A DUAL ROLE OF TLR2 AND MYD88 IN THEHOST DEFENSE AGAINST GBS SEPSIS ANDSTRONGLY SUGGEST TNF-ALPHA AS THE MOLECULARMEDIATOR OF BACTERIAL CLEARANCE AND SEPTICSHOCK.


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Titolo

INTERLEUKIN-18 IS AN ESSENTIAL ELEMENT IN HOSTRESISTANCE TO EXPERIMENTAL GROUP BSTREPTOCOCCAL DISEASE IN NEONATES.

Autori

V. CUSUMANO, A. MIDIRI, V. V. CUSUMANO, A.BELLANTONI, G. DE SOSSI, G. TETI, C. BENINATI ANDG. MANCUSO.

Abstract

PREVIOUS STUDIES DEMONSTRATED THATINTERLEUKIN-12 (IL-12)-DEPENDENT GAMMAINTERFERON (IFN-


INFECT IMMUN. 2004. 72:295-300.ANNO: 2004 - ISBN:

Titolo

HAEMOPHILUS INFLUENZAE PORIN INDUCES TOLL-LIKE RECEPTOR 2-MEDIATED CYTOKINEPRODUCTION IN HUMAN MONOCYTES AND MOUSEMACROPHAGE.

Autori


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GALDIERO M, GALDIERO M, FINAMORE E, ROSSANO F,GAMBUZZA M, CATANIA MR, TETI G, MIDIRI A,MANCUSO G.

Abstract

THE PRODUCTION OF PROINFLAMMATORYCYTOKINES IS LIKELY TO PLAY A MAJORPATHOPHYSIOLOGICAL ROLE IN MENINGITIS ANDOTHER INFECTIONS CAUSED BY HAEMOPHILUSINFLUENZAE TYPE B (HIB). PREVIOUS STUDIES HAVESHOWN THAT HIB PORIN CONTRIBUTES TOSIGNALING OF THE INFLAMMATORY CASCADE. WEEXAMINED HERE THE ROLE OF TOLL-LIKERECEPTORS (TLRS) AND THE TLR-ASSOCIATEDADAPTOR PROTEIN MYD88 IN HIB PORIN-INDUCEDPRODUCTION OF TUMOR NECROSIS FACTOR ALPHA(TNF-



Titolo

INDUCTION OF T HELPER TYPE 1 RESPONSES BY APOLYSACCHARIDE DEACETYLASE FROMCRYPTOCOCCUS NEOFORMANS.

Autori

BIONDO C, BENINATI C, BOMBACI M, MESSINA L,MANCUSO G, MIDIRI A, GALBO R, TETI G.

Abstract

A 25-KDA CRYPTOCOCCAL DEACETYLASE (D25) WASFOUND HERE TO INDUCE CELL PROLIFERATION, ASWELL AS SECRETION OF INTERLEUKIN 2 AND GAMMA


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INTERFERON, BUT NOT INTERLEUKIN 4, IN SPLEENCELLS FROM D25-IMMUNIZED OR CRYPTOCOCCUSNEOFORMANS-INFECTED MICE. THE GAMMAINTERFERON, BUT NOT THE INTERLEUKIN 2,RESPONSE WAS REQUIRED FOR THE PROTECTIVEACTIVITIES OF D25 IMMUNIZATION IN A MURINECRYPTOCOCCOSIS MODEL.



Titolo

IDENTIFICATION AND CLONING OF A CRYPTOCOCCALDEACETYLASE THAT PRODUCES PROTECTIVEIMMUNE RESPONSES.

Autori

BIONDO C., BENINATI C., DELFINO D., MANCUSO G.,MIDIRI A., BOMBACI M., TOMASELLI G., AND G. TETI.

Abstract

CELL-MEDIATED IMMUNITY PLAYS A CRUCIAL ROLE INHOST DEFENSES AGAINST CRYPTOCOCCUS(FILOBASIDIELLA) NEOFORMANS. THEREFORE, THEIDENTIFICATION OF CRYPTOCOCCAL ANTIGENSCAPABLE OF PRODUCING T-CELL-MEDIATEDRESPONSES, SUCH AS DELAYED-TYPEHYPERSENSITIVITY (DTH) REACTIONS, MAY BEUSEFUL IN THE DEVELOPMENT OF IMMUNE-BASEDSTRATEGIES TO CONTROL CRYPTOCOCCOSIS. INORDER TO CHARACTERIZE DTH-PRODUCINGANTIGENS, CULTURE SUPERNATANTS FROM THEUNENCAPSULATED CAP-67 STRAIN WERESEPARATED BY ANION-EXCHANGECHROMATOGRAPHY. AFTER FURTHERFRACTIONATION BY PREPARATIVE SODIUM DODECYLSULFATE-POLYACRYLAMIDE GEL ELECTROPHORESIS,A PURIFIED PROTEIN WITH AN APPARENT


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MOLECULAR MASS OF 25 KDA WAS FOUND TOPRODUCE DTH, AS EVIDENCED BY INCREASEDFOOTPAD SWELLING IN MICE IMMUNIZED WITHCULTURE SUPERNATANTS, RELATIVE TOUNIMMUNIZED MICE. THE 20-AMINO-ACID N-TERMINALSEQUENCE OF THE 25-KDA PROTEIN WAS USED TOSEARCH DATA OF THE C. NEOFORMANS GENOMEPROJECT. BASED ON THE GENOMIC DNA SEQUENCE,A DNA PROBE WAS USED TO SCREEN A


INFECT. IMMUN. 2002. 70:2383-2391.ANNO: 2002 - ISBN:

Titolo

MITOGEN-ACTIVATED PROTEIN KINASES AND NF-KBARE INVOLVED IN TNF-A RESPONSES TO GROUP BSTREPTOCOCCI

Autori

G. MANCUSO, A. MIDIRI, C. BENINATI, G. PIRAINO, A.VALENTI, G. NICOCIA, D. TETI, J. COOK AND G. TETI

Abstract

TNF-


JOURNAL OF IMMUNOLOGY 2002.169:1401-1409.ANNO: 2002 - ISBN:

Titolo

ANTI-IDIOTYPIC VACCINATION AGAINST GROUP BSTREPTOCOCCI.


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Autori

BENINATI C, OGGIONI M, MANCUSO G, MIDIRI A,POLONELLI L, POZZI G, TETI G.

Abstract

WE DESCRIBE THE ANTIGENIC PROPERTIES OF ANANTI-IDIOTYPIC SINGLE CHAIN FRAGMENT VARIABLE(SCFV) RECOMBINANT ANTIBODY MIMICKING THETYPE III CAPSULAR POLYSACCHARIDE OF GROUP BSTREPTOCOCCI (GBS), AN IMPORTANT CAUSE OFNEONATAL SEPSIS. THIS SCFV COULD COMPETEWITH THE NOMINAL ANTIGEN FOR BINDING TOSPECIFIC MOUSE OR RABBIT ANTIBODIES.MOREOVER, THE SCFV ELICITED, IN MICE, THEPRODUCTION OF ANTIBODIES WHICH REACTEDAGAINST THE TYPE ILI POLYSACCHARIDE ANDPASSIVELY PROTECTED NEONATAL PUPS FROM GBSDISEASE. MATERNAL IMMUNIZATION WITH THE SCFVALSO PROTECTED NEONATAL MICE AGAINST GBSINFECTION. NEXT, THE SCFV WAS EXPRESSED ONTHE SURFACE OF THE COMMENSAL BACTERIUMSTREPTOCOCCUS GORDONII. INTRAVAGINALINOCULATION OF MICE WITH THESE RECOMBINANTBACTERIA INDUCED SIGNIFICANT ELEVATIONS INSERUM TITERS OF ANTI-GBS TYPE III ANTIBODIES.THEREFORE, THE EXPRESSION SCFV IN COMMENSALBACTERIA MAY BE A CONVENIENT AND EFFECTIVEWAY OF DELIVERING ANTI-IDIOTYPIC VACCINES.


BENINATI C, OGGIONI M, MANCUSO G, MIDIRI A,POLONELLI L, POZZI G, TETI G.ANNO: 2001 - ISBN:

Titolo

BETA 2 INTEGRINS ARE INVOLVED IN CYTOKINERESPONSES TO WHOLE GRAM POSITIVE BACTERIA.


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Autori

M. CUZZOLA, G. MANCUSO, C. BENINATI, C. BIONDO, F.GENOVESE, F. TOMASELLO, T. H. FLO, T. ESPEVIK ANDG. TETI.

Abstract

PROINFLAMMATORY CYTOKINES HAVE AN IMPORTANTPATHOPHYSIOLOGIC ROLE IN SEPTIC SHOCK. CD14 ISINVOLVED IN CYTOKINE RESPONSES TO A NUMBEROF PURIFIED BACTERIAL PRODUCTS, INCLUDINGLPS. HOWEVER, LITTLE IS KNOWN OF MONOCYTERECEPTORS INVOLVED IN CYTOKINE RESPONSES TOWHOLE BACTERIA. TO IDENTIFY THESE RECEPTORS,HUMAN MONOCYTES WERE PRETREATED WITHDIFFERENT MABS AND TNF-


JOURNAL OF IMMUNOLOGY. 2000.164:5871-6.ANNO: 2000 - ISBN:

Titolo

HUMAN MONOCYTE RECEPTORS INVOLVED IN TUMORNECROSIS FACTOR RESPONSES TO GROUP BSTREPTOCOCCAL PRODUCTS.

Autori

M. CUZZOLA, G. MANCUSO, C. BENINATI, C. BIONDO, C.VON HUNOLSTEIN, G. OREFICI, T. ESPEVIK, T. H. FLOAND G. TETI.

Abstract

SEVERAL GROUP B STREPTOCOCCAL PRODUCTSHAVE BEEN PREVIOUSLY FOUND TO STIMULATE


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HUMAN MONOCYTES TO PRODUCE TUMOR NECROSISFACTOR ALPHA. IN ORDER TO IDENTIFY THERECEPTORS INVOLVED IN THESE RESPONSES,MONOCYTES WERE STIMULATED WITH PURIFIEDGROUP- OR TYPE-SPECIFIC CARBOHYDRATES ORLIPOTEICHOIC ACID IN THE PRESENCE OF ANTI-RECEPTOR MONOCLONAL ANTIBODIES, SOLUBLECD14, OR LIPOPOLYSACCHARIDE-BINDING PROTEIN.RESULTS INDICATE THAT CD14 PLAYS AN IMPORTANTROLE IN TUMOR NECROSIS FACTOR ALPHARESPONSES TO ALL OF THE STIMULI TESTED.MOREOVER, BOTH CD14 AND COMPLEMENTRECEPTOR TYPE 3 MAY BE INVOLVED IN RESPONSESTO THE GROUP-ANTIGEN.


INFECTION AND IMMUNITY. 2000. 68:994-998.ANNO: 2000 - ISBN:

Titolo

ROLE OF INTERLEUKIN 10 IN A NEONATAL MOUSELISTERIOSIS MODEL.

Autori

F. GENOVESE, G. MANCUSO, M. CUZZOLA, C. BIONDO,C. BENINATI, D. DELFINO AND G. TETI.

Abstract

THIS STUDY WAS UNDERTAKEN TO TEST THEHYPOTHESIS THAT ALTERED IL-10 PRODUCTIONPLAYS A ROLE IN THE INCREASED SUSCEPTIBILITYOF NEONATES TO LISTERIOSIS. PLASMA IL-10 LEVELSWERE MEASURED IN NEONATAL AND ADULT MICE ATVARIOUS TIMES AFTER INFECTION WITH LISTERIAMONOCYTOGENES. RELATIVE TO ADULTS, NEONATALMICE HAD MARKEDLY INCREASED IL-10 LEVELSEARLY IN THE COURSE OF INFECTION WITH LISTERIAUSING A 90% LETHAL DOSE. HIGHER NEONATAL IL-10RESPONSES WERE ALSO OBSERVED AFTER


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INJECTING ADULTS AND PUPS WITH EQUAL DOSESOF KILLED ORGANISMS. SPLENIC MACROPHAGESFROM NEONATES PRODUCED HIGHER IL-10 LEVELSTHAN THOSE OF ADULTS AFTER IN VITROSTIMULATION WITH KILLED BACTERIA, CONFIRMINGIN VIVO OBSERVATIONS. MOREOVER, IL-10BLOCKADE HAD DIFFERENTIAL EFFECTS INNEONATES AND ADULTS INFECTED WITH LIVELISTERIA. IN ADULT MICE, ANTI-IL-10 ABS DECREASEDBACTERIAL BURDEN EARLY IN THE COURSE OFINFECTION, BUT WERE NO LONGER EFFECTIVE AT 6DAYS OR LATER AFTER CHALLENGE. IN THE PUPS,HOWEVER, THE SAME TREATMENT HAD BENEFICIALEFFECTS BOTH EARLY AND LATE DURING INFECTIONAND RESULTED IN INCREASED SURVIVAL.COLLECTIVELY, OUR DATA SUGGEST THAT ANOVERPRODUCTION OF IL-10 BY MACROPHAGES MAYAT LEAST PARTIALLY EXPLAIN THE INCREASEDSUSCEPTIBILITY OF NEONATES TO LISTERIOSIS, ANDPROVIDE FURTHER EVIDENCE THAT CYTOKINEPRODUCTION IS DIFFERENT IN ADULTS ANDNEONATES.



Titolo

NEONATAL MOUSE IMMUNITY AGAINST GROUP BSTREPTOCOCCAL INFECTION BY MATERNALVACCINATION WITH RECOMBINANT ANTI-IDIOTYPES.

Autori

W. MAGLIANI, L. POLONELLI, S. CONTI, A. SALATI, P. F.ROCCA, V. CUSUMANO, G. MANCUSO & G. TETI.

Abstract

WE INVESTIGATED WHETHER IMMUNIZATION WITHRECOMBINANT ANTI-IDIOTYPIC ANTIBODY


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FRAGMENTS MIMICKING THE CONFORMATION OF THECAPSULAR ANTIGEN CAN PROTECT AGAINSTINFECTION BY GROUP B STREPTOCOCCUS, ANIMPORTANT NEONATAL PATHOGEN. SINGLE-CHAINFRAGMENT-VARIABLE ANTI-IDIOTYPES COMPETEDWITH THE TYPE III CARBOHYDRATE FOR BINDING TOTYPE-SPECIFIC ANTIBODIES AND ELICITED, IN MICE,THE PRODUCTION OF PROTECTIVEIMMUNOGLOBULINS REACTING AGAINST THE TYPE IIIPOLYSACCHARIDE. MOREOVER, MATERNALIMMUNIZATION WITH SOLUBLE OR PHAGE-DISPLAYEDFRAGMENTS PROTECTED NEONATAL MICE AGAINSTSTREPTOCOCCAL INFECTION. THESE DATA INDICATETHAT RECOMBINANT ANTI-IDIOTYPIC ANTIBODIESMAY BE USEFUL IN DEVELOPING PROTEIN IMAGES OFRELEVANT CARBOHYDRATE EPITOPES AND,ULTIMATELY, IN PREVENTING INFECTIONS BYENCAPSULATED BACTERIA.


NATURE MEDICINE, VOL. 4, P. 705-709, 1998ANNO: 1998 - ISBN:

Titolo

ROLE OF INTERLEUKIN 12 IN EXPERIMENTALNEONATAL SEPSIS CAUSED BY GROUP BSTREPTOCOCCI

Autori

MANCUSO G, CUSUMANO V, GENOVESE F, GAMBUZZAM, BENINATI C, TETI G

Abstract

CYTOKINES ARE SUSPECTED TO PLAY AN IMPORTANTROLE IN SYSTEMIC INFECTIONS BY GROUP BSTREPTOCOCCI (GBS), AN IMPORTANT CAUSE OFNEONATAL SEPSIS. THIS WORK WAS UNDERTAKEN TODETERMINE IF INTERLEUKIN 12 (IL-12) IS PRODUCEDIN MOUSE PUPS INFECTED WITH GBS AND HAS A


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ROLE IN THIS SEPSIS MODEL, IL-12 ELEVATIONSWERE MEASURED BY BOTH AN ENZYME-LINKEDIMMUNOSORBENT ASSAY AND A BIOASSAY IN PLASMASAMPLES OBTAINED FROM 12 TO 72 H AFTER GBSCHALLENGE, PRETREATMENT WITH NEUTRALIZINGANTI-IL-12 ANTIBODIES SIGNIFICANTLY INCREASEDLETHALITY AND BLOOD CFU (P < 0.05), CONVERSELY,EITHER PROPHYLACTICALLY OR THERAPEUTICALLYADMINISTERED RECOMBINANT IL-12 (RIL-12)SIGNIFICANTLY IMPROVED SURVIVAL TIME ANDDECREASED BLOOD CFU. SINCE THESE BENEFICIALEFFECTS WERE ASSOCIATED WITH INCREASEDSPLEEN GAMMA INTERFERON (IFN-GAMMA)PRODUCTION, WE EXAMINED WHETHER THE LATTERCYTOKINE MEDIATED THE OBSERVED RIL-12EFFECTS. PRETREATMENT WITH NEUTRALIZING ANTI-IFN-GAMMA MONOCLONAL ANTIBODIESSIGNIFICANTLY COUNTERACTED THE BENEFICIALEFFECTS OF RIL-12 ON LETHALITY. OUR DATAINDICATE THAT RIL-12 IS A POSSIBLE CANDIDATEFOR TREATMENT OF GBS SEPSIS AND THAT ITSACTIVITIES IN THIS MODEL ARE AT LEAST PARTIALLYMEDIATED BY IFN-GAMMA.


INFECT IMMUN. 1997 SEP;65(9):3731-5ANNO: 1997 - ISBN:

Titolo

ENDOTOXIN-INDUCED LETHALITY IN NEONATAL MICEIS COUNTERACTED BY INTERLEUKIN-10 (IL-10) ANDEXACERBATED BY ANTI-IL-10

Autori

NICOLETTI F, MANCUSO G, CILIBERTI FA, BENINATI C,CARBONE M, FRANCO S, CUSUMANO V.

Abstract

THE LETHAL EFFECTS OCCURRING IN NEONATAL


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(<24-H-OLD) BALB/C MICE AFTER CHALLENGE WITH 25MG OF LIPOPOLYSACCHARIDE (LPS) PER KG OF BODYWEIGHT WERE SIGNIFICANTLY COUNTERACTED BYPRETREATMENT WITH RECOMBINANTINTERLEUKIN-10 (RIL-10; 25 OR 50 NG/MOUSE).CONCORDANTLY, BLOCKAGE OF ENDOGENOUS IL-10WITH THE SXC1 MONOCLONAL ANTIBODY INCREASEDLPS-INDUCED MORTALITY. BOTH IL-10 AND SXC1MODULATED THE RELEASE OF TUMOR NECROSISFACTOR ALPHA (TNF-ALPHA) SO THAT, RELATIVE TOCONTROLS, PEAK TNF-ALPHA VALUES AFTER LPSCHALLENGE WERE DECREASED BY RIL-10 ANDINCREASED BY ANTI-IL-10.


CLIN DIAGN LAB IMMUNOL. 1997 SEP;4(5):607-10ANNO: 1997 - ISBN:

Titolo

NEONATAL HYPERSUSCEPTIBILITY TO ENDOTOXINCORRELATES WITH INCREASED TUMOR NECROSISFACTOR PRODUCTION IN MICE

Autori

CUSUMANO V, MANCUSO G, GENOVESE F, CUZZOLA M,CARBONE M, COOK JA, COCHRAN JB, TETI G.

Abstract

SEPTIC SHOCK IS A MAJOR CAUSE OF MORTALITY INNEONATES. THE HYPOTHESIS WAS TESTED THATNEONATAL AGE IS ASSOCIATED WITH ALTEREDSENSITIVITY TO SHOCK-INDUCING BACTERIALPRODUCTS OR PROINFLAMMATORY CYTOKINES (ORBOTH). MICE OF DIFFERENT AGES WEREINOCULATED WITH VARIOUS DOSES OFLIPOPOLYSACCHARIDE (LPS), SUPERANTIGENICSTAPHYLOCOCCAL ENTEROTOXIN B (SEB), ORRECOMBINANT TUMOR NECROSIS FACTOR-A (RTNF-A), ALONE OR IN COMBINATION WITH THE


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SENSITIZING AGENT D-GALACTOSAMINE. NEONATALMICE WERE MARKEDLY MORE SUSCEPTIBLE TO LPS-INDUCED LETHALITY BUT MORE RESISTANT TO SEBTHAN WERE ADULTS (P .05). MICE OF DIFFERENTAGES DID NOT DIFFER, HOWEVER, IN THEIRSENSITIVITY TO LETHAL ACTIVITIES OF RTNFA.NEONATAL SUSCEPTIBILITY TO LPS AND SEBCORRELATED DIRECTLY WITH PLASMA TNF-A BUTNOT IFN-G LEVELS, WHICH WAS CONFIRMED BYTNF-A AND IFN-G BLOCKADE EXPERIMENTS. THESEDATA DOCUMENT MARKED AGE-RELATEDDIFFERENCES IN THE PATHOPHYSIOLOGY OF SEPTICSHOCK AND SUGGEST THAT IFN-G IS NOT ANOBLIGATORY MEDIATOR OF EITHER LPS- OR SEB-INDUCED LETHALITY IN NEONATES.


J INFECT DIS. 1997 JUL;176(1):168-76.ANNO: 1997 - ISBN:

Titolo

PORINS OF PSEUDOMONAS AERUGINOSA INDUCERELEASE OF TUMOR NECROSIS FACTOR ALPHA ANDINTERLEUKIN-6 BY HUMAN LEUKOCYTES

Autori

CUSUMANO V, TUFANO MA, MANCUSO G, CARBONE M,ROSSANO F, FERA MT, CILIBERTI FA, RUOCCO E,MERENDINO RA, TETI G.

Abstract

THE AIM OF THIS STUDY WAS TO EXAMINE THEABILITY OF PSEUDOMONAS AERUGINOSACOMPONENTS TO INDUCE RELEASE OF CYTOKINESFROM HUMAN LEUKOCYTES. HUMAN WHOLE-BLOODCULTURES WERE INCUBATED WITH SEVERALCONCENTRATIONS OF PURIFIED P. AERUGINOSAPRODUCTS, INCLUDING PORINS,EXOMUCOPOLYSACCHARIDE, LIPOPOLYSACCHARIDE,


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AND TOXIN A. SUPERNATANTS WERE ASSAYED FORTUMOR NECROSIS FACTOR ALPHA (TNF-A) ANDINTERLEUKIN-6 (IL-6) ACTIVITIES. ALL OF THE P.AERUGINOSA COMPONENTS EXCEPT TOXIN A WEREABLE TO STIMULATE THE RELEASE OF BOTHCYTOKINES. ON A WEIGHT BASIS, PORINS WERE ASEFFECTIVE AS LIPOPOLYSACCHARIDE ANDSIGNIFICANTLY MORE EFFECTIVE THANEXOMUCOPOLYSACCHARIDE IN INDUCING IL-6RELEASE (P < 0.05). MOREOVER, PORINS WERE MOREPOTENT THAN EITHER EXOMUCOPOLYSACCHARIDEOR LIPOPOLYSACCHARIDE IN INDUCING TNF-ARELEASE (P < 0.05). FURTHER EXPERIMENTS USINGISOLATED LEUKOCYTES SUGGESTED THATMONOCYTES WERE THE CELL POPULATIONPREDOMINANTLY RESPONSIBLE FOR THEPRODUCTION OF BOTH CYTOKINES. THESE DATAINDICATE THAT P. AERUGINOSA PORINS ARE ABLE TOINDUCE SIGNIFICANT CYTOKINE PRODUCTION. THESECOMPONENTS MAY BE RESPONSIBLE FOR THECHRONICALLY OVERACTIVE INFLAMMATORYRESPONSE ASSOCIATED WITH PERSISTENT LUNGINFECTION IN CYSTIC FIBROSIS PATIENTS.


INFECT IMMUN. 1997 MAY;65(5):1683-7.ANNO: 1997 - ISBN:

Titolo

SOLUBLE ANTIGENS FROM GROUP B STREPTOCOCCIINDUCE CYTOKINE PRODUCTION IN HUMAN BLOODCULTURES

Autori

VON HUNOLSTEIN C, TOTOLIAN A, ALFARONE G,MANCUSO G, CUSUMANO V, TETI G, OREFICI G.

Abstract

GROUP B STREPTOCOCCAL ANTIGENS STIMULATED


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TUMOR NECROSIS FACTOR ALPHA (TNF-A),INTERLEUKIN-1 (IL-1), AND IL-6 PRODUCTION INHUMAN BLOOD CULTURES IN A CONCENTRATION- ANDTIME-DEPENDENT FASHION. THE MINIMALCONCENTRATIONS OF TYPE-SPECIFICPOLYSACCHARIDES, LIPOTEICHOIC ACID, ANDGROUP-SPECIFIC POLYSACCHARIDE REQUIRED TOPRODUCE THESE EFFECTS WERE, RESPECTIVELY,0.01, 1, AND 10 MG/ML. CELL SEPARATIONEXPERIMENTS INDICATED THAT MONOCYTES WERETHE CELL TYPE MAINLY RESPONSIBLE FOR CYTOKINEPRODUCTION. TIME COURSE STUDIES INDICATEDTHAT TNF-A WAS RELEASED BEFORE THE OTHERCYTOKINES. TNF-A, HOWEVER, DID NOT APPEAR TODIRECTLY INDUCE IL-1B, AS SHOWN BY BLOCKADEEXPERIMENTS WITH ANTI-TNF-A ANTIBODIES. IL-6LEVELS WERE MODERATELY BUT SIGNIFICANTLYDECREASED BY ANTI-TNF-A. THESE DATA INDICATETHAT SEVERAL PRODUCTS FROM GROUP BSTREPTOCOCCI ARE ABLE TO DIRECTLY STIMULATEHUMAN MONOCYTES TO RELEASE TNF-A, IL-1B, ANDIL-6. THESE FINDINGS MAY BE CLINICALLY RELEVANT,SINCE PROINFLAMMATORY CYTOKINES CAN MEDIATEPATHOPHYSIOLOGIC CHANGES DURING SEPSIS.


INFECT IMMUN. 1997 OCT;65(10):4017-21.ANNO: 1997 - ISBN:

Titolo

PREVENTION OF ENDOTOXIN-INDUCED LETHALITY INNEONATAL MICE BY INTERLEUKIN-13

Autori

NICOLETTI F, MANCUSO G, CUSUMANO V, DI MARCO R,ZACCONE P, BENDTZEN K, TETI G.

Abstract

NICOLETTI F, MANCUSO G, CUSUMANO V, DI MARCO R,


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ZACCONE P, BENDTZEN K, TETI G.


EUR J IMMUNOL. 1997 JUN;27(6):1580-3.ANNO: 1997 - ISBN:

Titolo

AGE-RELATED SENSITIVITY OF NEONATAL MICE TOTOXICITY INDUCED BY HEAT-KILLED GROUP BSTREPTOCOCCI.

Autori

TETI G, MANCUSO G, LOSI E, TOMASELLO F,CUSUMANO V, GAMBUZZA M, PETRELLI ML.

Abstract


ADV EXP MED BIOL. 1997;418:945-7.ANNO: 1997 - ISBN:

Titolo

ROLE OF GAMMA INTERFERON IN A NEONATALMOUSE MODEL OF GROUP B STREPTOCOCCALDISEASE

Autori

CUSUMANO V, MANCUSO G, GENOVESE F, DELFINO D,BENINATI C, LOSI E, TETI G.


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Abstract

THE AIM OF THIS STUDY WAS TO ASSESS THE ROLEOF GAMMA INTERFERON (IFN-GAMMA) IN A NEONATALMOUSE MODEL OF GROUP B STREPTOCOCCAL (GBS)SEPSIS. IFN-GAMMA WAS PRODUCED BY SPLEENCELLS AT 24, 48, AND 72 H AFTER GBS CHALLENGE,TREATMENT WITH ANTI-IFN-GAMMA AT 6 H BEFORECHALLENGE TOTALLY ABROGATED THE IFN-GAMMARESPONSE BUT DID NOT AFFECT SURVIVAL.SUBCUTANEOUS ADMINISTRATION OF RECOMBINANTIFN-GAMMA (2,500 IU PER PUP) AT 18 H AFTERCHALLENGE RESULTED IN INCREASED SURVIVALTIME AND REDUCED BLOOD COLONY COUNTS AT 48AND 72 H. IN VITRO PREINCUBATION OF NEONATALWHOLE BLOOD WITH IFN-GAMMA BEFORE THEADDITION OF GBS RESULTED IN SIGNIFICANTRESTRICTION OF BACTERIAL GROWTH. THESE DATAINDICATE THAT ADMINISTRATION OF RECOMBINANTIFN-GAMMA CAN PARTIALLY RESTORE IMPAIREDHOST DEFENSES AGAINST GBS IN NEONATAL MICE.THIS CYTOKINE MAY BE USEFUL FOR THE TREATMENTOF NEONATAL INFECTION


INFECT IMMUN. 1996 AUG;64(8):2941-4.ANNO: 1996 - ISBN:

Titolo

INTERLEUKIN-10 PROTECTS NEONATAL MICE FROMLETHAL GROUP B STREPTOCOCCAL INFECTION

Autori

CUSUMANO V, GENOVESE F, MANCUSO G, CARBONEM, FERA MT, TETI G.

Abstract


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WE INVESTIGATED THE ROLE OF INTERLEUKIN-10(IL-10) IN A NEONATAL MOUSE MODEL OF LETHALGROUP B STREPTOCOCCI (GBS) SEPSIS. PLASMAIL-10 LEVELS SIGNIFICANTLY INCREASED AT 24 AND48 H AFTER GBS INOCULATION. NEUTRALIZATION OFIL-10 WITH SPECIFIC ANTIBODIES HAD NO EFFECT ONLETHALITY. ADMINISTRATION OF RECOMBINANT IL-10AT 20 OR 4 H BEFORE CHALLENGE, BUT NOT ATLATER TIMES, RESULTED IN DECREASED TUMORNECROSIS FACTOR ALPHA LEVELS AND IMPROVEDSURVIVAL. IL-10 COULD BE POTENTIALLY USEFULFOR THE TREATMENT OF GBS SEPSIS.


INFECT IMMUN. 1996 JUL;64(7):2850-2.ANNO: 1996 - ISBN:

Titolo

IMMUUOBIOLOGICAL ACTIVITIES OF MOULDPRODUCTS: FUNCTIONAL IMPAIRMENT OF HUMANMONOCYTES EXPOSED TO AFLATOXIN B-1

Autori

CUSUMANO V, ROSSANO F, MERENDINO RA, ARENA A,COSTA GB, MANCUSO G, BARONI A, LOSI E.

Abstract

IN ORDER TO ELUCIDATE THE EFFECTS UPON THEHUMAN IMMUNE SYSTEM OF AFLATOXIN B1PRODUCED BY THE FOOD-CONTAMINATING MOULDASPERGILLUS FLAVUS, PHAGOCYTOSIS,MICROBICIDAL ACTIVITY, SUPEROXIDE PRODUCTIONAND INTRINSIC ANTIVIRAL ACTIVITY WERE STUDIEDIN MONOCYTES EXPOSED TO AFLATOXIN B1 FORDIFFERENT TIMES AT CONCENTRATIONS RANGINGFROM 0.1 TO 1 PG/ML. PHAGOCYTOSIS ANDMICROBICIDAL ACTIVITY WERE SIGNIFICANTLYIMPAIRED (P < 0.05) BY AFLATOXIN B1 AT DOSES AS


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LOW AS 0.1 PG/ML. HOWEVER, PRETREATMENT OFMONOCYTES WITH AFLATOXIN B1 DID NOT MODIFYINTRINSIC ANTIVIRAL ACTIVITY OR SUPEROXIDEPRODUCTION. THESE RESULTS CONFIRMED DATAOBTAINED FROM ANIMALS FED WITH MYCOTOXIN-CONTAMINATED FOODS. THE POTENTIAL DANGER TOHUMAN HEALTH OF EXPOSURE TO MYCOTOXINSDEMONSTRATES THE NECESSITY FOR CAREFULMICROBIOLOGICAL CONTROL OF FOOD.


RES MICROBIOL. 1996 JUN;147(5):385-91ANNO: 1996 - ISBN:

Titolo

TUMOR NECROSIS FACTOR-INDUCING ACTIVITIES OFCRYPTOCOCCUS NEOFORMANS COMPONENTS

Autori

DELFINO D, CIANCI L, MIGLIARDO M, MANCUSO G,CUSUMANO V, CORRADINI C, TETI G.

Abstract

CRYPTOCOCCUS NEOFORMANS-INDUCED TUMORNECROSIS FACTOR ALPHA (TNF-A) PRODUCTION MAYLEAD TO INCREASED HUMAN IMMUNODEFICIENCYVIRUS REPLICATION IN PATIENTS WITH AIDS. INORDER TO IDENTIFY CRYPTOCOCCAL COMPONENTSTHAT ARE PREDOMINANTLY RESPONSIBLE FORSTIMULATING TNF PRODUCTION, VARIOUSCONCENTRATIONS OF GLUCURONOXYLOMANNAN(GXM), GALACTOXYLOMANNAN (GALXM),MANNOPROTEINS (MP), AND B(1-3) GLUCAN WEREADDED TO WHOLE-BLOOD CULTURES. ALL OF THECRYPTOCOCCAL COMPONENTS TESTED, AS WELL ASWHOLE HEAT-KILLED CRYPTOCOCCI, WERE CAPABLEOF INDUCING TNF-A RELEASE IN A DOSE-DEPENDENTMANNER. MP WERE SIGNIFICANTLY MORE POTENTTHAN ANY OF THE OTHER CRYPTOCOCCAL


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COMPONENTS TESTED OR HEAT-KILLEDCRYPTOCOCCI IN STIMULATING TNF-A PRODUCTION(P < 0.05). GXM, IN CONTRAST, WAS SIGNIFICANTLYLESS POTENT IN THIS ACTIVITY THAN EITHER GALXMOR MP (P < 0.05). AS LITTLE AS 0.5 MG OF MP PER MLWAS SUFFICIENT TO PRODUCE MODERATE BUTSIGNIFICANT ELEVATIONS OF TNF-A RELEASE.MAXIMAL MP-INDUCED TNF-A LEVELS WERE SIMILARTO THOSE INDUCED BY SALMONELLA ENTERITIDISLIPOPOLYSACCHARIDE, OUR POSITIVE CONTROL.FURTHER EXPERIMENTS USING ISOLATEDLEUKOCYTES SUGGESTED THAT MONOCYTES WERETHE CELL POPULATION MAINLY RESPONSIBLE FORTNF-A PRODUCTION, ALTHOUGH THE PARTICIPATIONOF OTHER CELL TYPES COULD NOT BE EXCLUDED.THE PRESENCE OF COMPLEMENT-SUFFICIENTPLASMA WAS A NECESSARY REQUIREMENT FORTNF-A INDUCTION BY GXM, GALXM, AND LOW DOSESOF MP. HIGH MP CONCENTRATIONS (100 MG/ML) WEREALSO CAPABLE OF STIMULATING TNF-A PRODUCTIONIN THE ABSENCE OF PLASMA. THESE DATA INDICATETHAT SOLUBLE PRODUCTS RELEASED BY C.NEOFORMANS ARE CAPABLE OF INDUCING TNF-ASECRETION IN HUMAN LEUKOCYTES. THIS MAY BECLINICALLY RELEVANT, SINCE HIGHCONCENTRATIONS OF SUCH PRODUCTS AREFREQUENTLY FOUND IN THE BODY FLUIDS OF AIDSPATIENTS INFECTED WITH C. NEOFORMANS.


INFECT IMMUN. 1996 DEC;64(12):5199-204.ANNO: 1996 - ISBN:

Titolo

IMPROVED SURVIVAL AND ANTAGONISTIC EFFECT OFSODIUM FUSIDATE ON TUMOR NECROSIS FACTORALPHA IN A NEONATAL MOUSE MODEL OF ENDOTOXINSHOCK

Autori

GENOVESE F, MANCUSO G, CUZZOLA M, CUSUMANO V,


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NICOLETTI F, BENDTZEN K, TETI G.

Abstract

UNLIKE THE ANTIBIOTICS ERYTHROMYCIN ANDPENICILLIN G, SODIUM FUSIDATE (FUSIDIN)PRETREATMENT (80 MG/KG OF BODY WEIGHT)INCREASED THE SURVIVAL RATE OF NEONATALBALB/C MICE CHALLENGED WITH SALMONELLAENTERITIDIS LIPOPOLYSACCHARIDE. FUSIDIN ALSOSIGNIFICANTLY REDUCED THE PLASMA TUMORNECROSIS FACTOR ALPHA LEVELS. HENCE, FUSIDINMAY PROVE USEFUL IN THE MANAGEMENT OFBACTERIAL SEPSIS IN HUMANS.


ANTIMICROB AGENTS CHEMOTHER. 1996JUL;40(7):1733-5.ANNO: 1996 - ISBN:

Titolo

EFFECTS OF TAXOL ON TNF-ALPHA AND IL-6PRODUCTION BY HUMAN PERIPHERAL BLOOD CELLS

Autori

LOSI E, ROSSANO F, CUSUMANO V, MANCUSO G,TOMASELLO F, CHILLEMI S, PASTURA G, TRIFILETTI R,TETI G, MERENDINO RA.

Abstract

TAXOL, A NEW DRUG ISOLATED FROM THE BARK OFTHE PACIFIC YEW TREE, IS BEING USED IN TREATINGPATIENTS WITH BREAST, OVARY, LUNG, NECK, ANDBRAIN CANCER.’.* THE THERAPEUTIC MECHANISMSOF TAXOL ARE NOT YET COMPLETELY KNOWN. TAXOLBINDS TO P-TUBULIN, STABILIZES MICROTUBULESAGAINST DEP~LYMERIZATIONA,~N D INTERFERES


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WITH MICROTUBULES DURING THE CELL DIVISIONS,BLOCKING THE CELL THROUGH ME T APHA~EP.R~OBABLY, MICROTUBULES ARE NOT THE ONLY TARGETSOF THIS DRUG. ON MURINE MACROPHAGES, TAXOLAPPEARS TO HAVE AN ACTION SIMILAR TO THAT OFBACTERIAL LIPOPOLYSACCHARIDE (LPS). THERE ISSOME EVIDENCE THAT THE DRUG BINDS TORECEPTORS PROXIMAL TO THOSE OF LPS.’ LPSACTIVATES ANTITUMOR MECHANISMS SUCH ASBIOSYNTHESIS OF TUMOR NECROSIS FACTOR ALPHA(TNF-CY)A~N,D~ DIRECT MACROPHAGE TUMORICIDALACTIVITY.8 THUS, THE ANTITUMOR ACTIVITIES OFTAXOL MAY BE IN PART RELATED TO ITS ABILITY TOSTIMULATE MACROPHAGES. THE OBJECTIVE OF THISSTUDY WAS TO DETERMINE IF CELLS FROM THEPERIPHERAL BLOOD OF HEALTHY DONORS ORTUMOR PATIENTS CAN BE STIMULATED WITH TAXOLTO PRODUCE TNF-A OR IL-6 DIRECTLY OR IN THEPRESENCE OF “PRIMING” SIGNALS, SUCH AS THOSEPROVIDED BY INTERFERON-GAMMA (IFN-Y).


ANN N Y ACAD SCI. 1996 APR 30;784:525-8ANNO: 1996 - ISBN:

Titolo

EFFECTS OF ANTI-CYTOKINE TREATMENTS INNEONATAL SEPSIS MODELS

Autori

TETI G, MANCUSO G, CUSUMANO V, BLANDINO G,FERA MT, CARBONE M.

Abstract



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J CHEMOTHER. 1995 NOV;7 SUPPL 4:96-8.ANNO: 1995 - ISBN:

Titolo

FUNCTIONAL IMPAIRMENT OF RAT KUPFFER CELLSINDUCED BY AFLATOXIN B-1 AND ITS METABOLITES

Autori

CUSUMANO V, COSTA GB, TRIFILETTI R, MERENDINORA, MANCUSO G.

Abstract

CONTAMINATION OF FOOD WITH MYCOTOXINS IS AMAJOR HEALTH PROBLEM. IMPAIRMENT OF SEVERALIMMUNE FUNCTIONS HAS BEEN REPEATEDLYREPORTED IN ANIMALS FED WITH CONTAMINATEDFODDER. SINCE THE LIVER IS A MAJOR TARGET OFTOXICITY BY AFLATOXINS, THE EFFECTS OFAFLATOXINS B1, AND ITS HEPATIC METABOLITES Q1AND M1 ON KUPFFER CELL FUNCTION WASINVESTIGATED IN VITRO. AFLATOXIN B1 INDUCEDSIGNIFICANT (P < 0.05) INHIBITION OFPHAGOCYTOSIS, INTRACELLULAR KILLING OFCANDIDA ALBICANS, AND INTRINSIC ANTI-HERPESVIRUS ACTIVITY AT CONCENTRATIONS AS LOW AS0.01 PG ML-1. AFLATOXIN Q1 AND M1 HAD SIMILAREFFECTS ON PHAGOCYTOSIS AND MICROBICIDALACTIVITY, BUT WERE TWO- TO TEN-FOLD LESSPOTENT THAN AFLATOXIN B1.


FEMS IMMUNOL MED MICROBIOL. 1995JAN;10(2):151-5.ANNO: 1995 - ISBN:

Titolo


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BENEFICIAL-EFFECTS OF PENTOXIFYLLINE INNEONATAL RATS INFECTED WITH GROUP-BSTREPTOCOCCI

Autori

MANCUSO G, BLANDINO G, GAMBUZZA M, GENOVESEF, MIGLIARDO M, CARBONE M, FERA MT, CUSUMANO V.

Abstract

PREVIOUS STUDIES HAVE INDICATED THAT TUMORNECROSIS FACTOR-ALPHA (TNF-ALPHA) MAY PLAY APATHOPHYSIOLOGIC ROLE IN EXPERIMENTAL SEPSISBY GROUP B STREPTOCOCCI (GBS). WE TESTED THEEFFICACY OF SOME TNF-ALPHA AND EICOSANOIDINHIBITORS IN A NEONATAL RAT MODEL OF GBSDISEASE. THE DRUGS TESTED INCLUDEDCLORICROMENE, SKF86002, PENTOXIFYLLINE,CGS8515, IBUPROFEN AND LY203647. NONE OF THESECOMPOUNDS WERE PROTECTIVE AGAINST GBSINFECTION, WITH THE EXCEPTION OFPENTOXIFYLLINE, THAT PRODUCED A MODERATEENHANCEMENT OF SURVIVAL TIME. FURTHERSTUDIES ARE NEEDED TO ASCERTAIN IF SPECIFICINHIBITORS OF TNF-ALPHA, ALONE OR INCONJUNCTION WITH ANTIBIOTICS, MAY BEEFFECTIVE AS THERAPEUTIC AGENTS IN NEONATALGBS SEPSIS.


J CHEMOTHER. 1995 OCT;7(5):417-9.ANNO: 1995 - ISBN:

Titolo

BENEFICIAL-EFFECTS OF INTERLEUKIN-6 INNEONATAL MOUSE MODELS OF GROUP-BSTREPTOCOCCAL DISEASE


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Autori

MANCUSO G, TOMASELLO F, MIGLIARDO M, DELFINOD, COCHRAN J, COOK JA, TETI G.

Abstract

PREVIOUS STUDIES HAVE SHOWN THAT TUMORNECROSIS FACTOR ALPHA (TNF-A) PLAYS APATHOPHYSIOLOGIC ROLE IN SEPSIS INDUCED INRAT PUPS BY GROUP B STREPTOCOCCI (GBS). INTHIS MODEL, TNF-A IS ALSO PARTIALLYRESPONSIBLE FOR THE INDUCTION OFINTERLEUKIN-6 (IL-6). THE PRESENT STUDY WASUNDERTAKEN TO INVESTIGATE THE ROLE OF IL-6 INNEONATAL BALB/C MICE INFECTED WITH TYPE IIIGBS. THE EFFECT OF ANTI-IL-6 MONOCLONALANTIBODIES AND RECOMBINANT IL-6 ON LETHALITYAND TNF-A PRODUCTION WAS INVESTIGATED. INMOUSE PUPS INFECTED WITH GBS STRAIN COH1,PLASMA IL-6 REACHED LEVELS OF 3,067 ± 955 AND1,923 ± 891 U/ML WHEN MEASURED AT 22 AND 48 H,RESPECTIVELY (P < 0.05 COMPARED WITHUNINFECTED CONTROLS). PRETREATMENT WITH 25,UG OF ANTI-IL-6 ANTIBODIES TOTALLY PREVENTEDTHE INCREASE IN CIRCULATING IL-6 BIOACTIVITY ATBOTH 22 AND 48 H AFTER INFECTION (P < 0.05).TREATMENT WITH ANTI-IL-6 ALSO INDUCED AMODERATE DECREASE IN SURVIVAL TIME OF MICEINFECTED WITH LETHAL DOSES OF STRAINS COHIAND COH31, AS EVIDENCED BY INCREASEDLETHALITY (P < 0.05) AT 24 TO 48 H BUT NOT AT 96 H.MOUSE RECOMBINANT IL-6 (12,500 U) GIVEN 6 HBEFORE CHALLENGE WITH STRAINS COH1 ANDCOH31 CONSISTENTLY INCREASED SURVIVAL TIME,AS EVIDENCED BY DECREASED (P < 0.05) LETHALITYAT 48 TO 72 H BUT NOT AT 96 H. THE EFFECTS OF IL-6PRETREATMENT WERE DOSE DEPENDENT, SINCE NOPROTECTION WAS OBSERVED WITH DOSES LOWERTHAN 12,500 U. IN ADDITION, NO EFFECTS ONLETHALITY WERE NOTED WHEN II-6 WAS GIVEN ATTHE TIME OF CHALLENGE OR AT LATER TIMES. TNF-AELEVATIONS (P < 0.05 COMPARED WITH UNINFECTEDCONTROLS) WERE MEASURED AT 12, 22, AND 48 HAFTER CHALLENGE WITH STRAIN COH1 (68 ± 28, 233 +98, AND 98 ± 34 U, RESPECTIVELY). PRETREATMENT


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WITH IL-6 SIGNIFICANTLY (P < 0.05) DECREASEDPLASMA TNF-A LEVELS AT 12 AND 22 H, WITH 55 AND69%V INHIBITIONS, RESPECTIVELY. ANTI-IL-6 HAD ANOPPOSITE EFFECT, AS EVIDENCED BY A 145%INCREASE (P < 0.05) IN TNF-A LEVELS AT 48 H AFTERCHALLENGE. COLLECTIVELY, OUR DATA ARECOMPATIBLE WITH THE HYPOTHESIS THAT IL-6 ISINVOLVED IN NEGATIVE FEEDBACK REGULATION OFPLASMA TNF-A LEVELS IN EXPERIMENTAL GBSSEPSIS. IN THIS MODEL, IL-6 PRETREATMENT CANINCREASE SURVIVAL TIME. FUTURE STUDIES WILL BENEEDED TO INVESTIGATE THE MECHANISMSUNDERLYING THIS EFFECT.


INFECT IMMUN. 1994 NOV;62(11):4997-5002.ANNO: 1994 - ISBN:

Titolo

EFFICACY OF TUMOR-NECROSIS-FACTOR-ALPHA ANDEICOSANOID INHIBITORS IN EXPERIMENTAL-MODELSOF NEONATAL SEPSIS

Autori

MANCUSO G, CUSUMANO V, COOK JA, SMITH E,SQUADRITO F, BLANDINO G, TETI G.

Abstract

THE POTENTIAL ROLE OF TUMOR NECROSIS FACTORALPHA (TNF ALPHA) AND EICOSANOIDS IN THEPATHOGENESIS OF EXPERIMENTAL NEONATALSEPSIS MODELS WAS INVESTIGATED. LETHALITYWAS INDUCED IN NEONATAL RATS BYADMINISTRATION OF HEAT KILLED GROUP BSTREPTOCOCCI (GBS, 7 MG KG-1 INTRACARDIALLY)OR SALMONELLA ENTERITIDIS ENDOTOXIN (0.35 MGKG-1 INTRACARDIALLY). THE RELATIVE EFFICACY OFSIX COMPOUNDS WITH PUTATIVE TNF ALPHA ANDEICOSANOID INHIBITORY ACTIONS WERE TESTED.


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THESE WERE: IBUPROFEN (3 AND 20 MG KG-1), ACYCLO-OXYGENASE INHIBITOR; CGS85515 (30 MGKG-1), A LIPOXYGENASE INHIBITOR; LY203647 (30 MGKG-1), A LEUKOTRIENE D4 RECEPTOR ANTAGONIST;PENTOXIFYLLINE (10, 50 AND 100 MG KG-1), A TNFINHIBITOR; CLORICROMENE (2 AND 10 MG KG-1), ATHROMBOXANE A2 SYNTHETASE INHIBITOR WITH TNFALPHA INHIBITORY ACTIONS; AND SKF86002 (2.5, 5, 10AND 20 MG KG-1), A DUAL CYCLO-OXYGENASE/LIPOXYGENASE INHIBITOR WITH TNFALPHA INHIBITORY ACTIVITY. PENTOXIFYLLINE,CLORICROMENE AND SKF86002, WHEN GIVENINTRAPERITONEALLY 2 H BEFORE CHALLENGE,PRODUCED 45, 52 AND 61% REDUCTIONS,RESPECTIVELY, IN PLASMA LEVELS OF TNF ALPHA AT2.5 H POST-INJECTION WITH KILLED GBS (P < 0.05). ONTHE CONTRARY, PRETREATMENT WITH IBUPROFEN,CGS85515 OR LY203647 DID NOT SIGNIFICANTLYAFFECT TNF ALPHA LEVELS. ALL COMPOUNDSSIGNIFICANTLY ATTENUATED THE LETHALITY BYKILLED GBS AND S. ENTERITIDIS ENDOTOXIN. THESEDATA SUGGEST THAT TNF ALPHA AND EICOSANOIDSCONTRIBUTE TO THE PATHOGENESIS OF SHOCKINDUCED BY KILLED GBS AND ENDOTOXEMIA. PMID:7920463


FEMS IMMUNOL MED MICROBIOL. 1994 JUN;9(1):49-54.ANNO: 1994 - ISBN:

Titolo

EFFECTS OF LITHIUM-CARBONATE ON CYTOKINEPRODUCTION IN PATIENTS AFFECTED BY BREAST-CANCER

Autori

MERENDINO RA, MANCUSO G, TOMASELLO F,GAZZARA D, CUSUMANO V, CHILLEMI S, SPADARO P,MESITI M.


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Abstract

IT HAS BEEN REPORTED THAT LITHIUM SALTCOMPOUNDS INFLUENCE HEMATOPOIESIS, WHICH ISKNOWN TO BE REGULATED BY A NUMBER OFCYTOKINES, INCLUDING TUMOR NECROSIS FACTOR(TNF), INTERLEUKIN-1 (IL-1) AND INTERLEUKIN-6 (IL-6).SINCE LITHIUM CAN INDUCE TNF PRODUCTION INHUMAN MONOCYTES, WE WISHED TO DETERMINE IFLITHIUM CARBONATE TREATMENT OF NEUTROPENICPATIENTS AFFECTED BY BREAST CANCER RESULTSIN INCREASED CYTOKINE PRODUCTION. SERUMLEVELS OF TNF ALPHA, IL-1 AND IL-6 WEREMEASURED BEFORE AND AT 7 AND 180 DAYS AFTERTREATMENT WITH LITHIUM CARBONATE. RESULTSINDICATE THAT THIS THERAPY PRODUCED TNFALPHA AND IL-6, BUT NOT IL-1 ALPHA, ELEVATIONS INPATIENTS AFFECTED BY UNMETASTASIZED BREASTCANCER. CONVERSELY, TNF ALPHA, BUT NOT IL-6,ELEVATIONS WERE DETECTED IN METASTATICPATIENTS. STUDIES ARE UNDER WAY TOINVESTIGATE THE MECHANISMS BY WHICH LITHIUMSALTS AFFECT CYTOKINE PRODUCTION INMONOCYTES FROM CANCER PATIENTS.


J BIOL REGUL HOMEOST AGENTS. 1994 JUL-SEP;8(3):88-91.ANNO: 1994 - ISBN:

Titolo

ANTI-LIPOTEICHOIC ACID ANTIBODIES ENHANCERELEASE OF CYTOKINES BY MONOCYTESSENSITIZED WITH LIPOTEICHOIC ACID

Autori

MANCUSO G, TOMASELLO F, OFEK I, TETI G.

Abstract


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LIPOTEICHOIC ACID (LTA) FROM GRAM-POSITIVEBACTERIA CAN STIMULATE MONOCYTES TOPRODUCE CYTOKINES. TO ASCERTAIN WHETHERAGGREGATION OF LTA RECEPTORS CANCONTRIBUTE TO THIS EFFECT, HUMAN MONOCYTESWERE SENSITIZED WITH LTA FROMSTREPTOCOCCUS PYOGENES, WASHED, ANDTREATED WITH ANTI-LTA ANTIBODIES. THE ADDITIONOF ANTI-LTA ANTIBODIES OR F(AB')2 FRAGMENTSMARKEDLY ENHANCED THE AGGREGATION OF LTARECEPTORS, AS EVIDENCED BY INDIRECTIMMUNOFLUORESCENCE AND THE RELEASE OFTUMOR NECROSIS FACTOR ALPHA ANDINTERLEUKIN-1 BETA. THESE FINDINGS SUGGESTTHAT AGGREGATION OF LTA RECEPTORS OFMONOCYTES IS REQUIRED FOR TRIGGERINGMARKED CYTOKINE RESPONSES.


INFECT IMMUN. 1994 APR;62(4):1470-3.ANNO: 1994 - ISBN:

Titolo

INDUCTION OF TUMOR-NECROSIS-FACTOR-ALPHA BYTHE GROUP-SPECIFIC AND TYPE-SPECIFICPOLYSACCHARIDES FROM TYPE-III GROUP-BSTREPTOCOCCI

Autori

MANCUSO G, TOMASELLO F, VON HUNOLSTEIN C,OREFICI G, TETI G.

Abstract

PREVIOUS STUDIES SUGGESTED THAT CIRCULATINGTUMOR NECROSIS FACTOR ALPHA (TNF-ALPHA) MAYHAVE A PATHOPHYSIOLOGIC ROLE IN EXPERIMENTALNEONATAL SEPSIS INDUCED BY GROUP BSTREPTOCOCCI (GBS). THIS STUDY WAS


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UNDERTAKEN TO INVESTIGATE THE ABILITY OF THETYPE III AND GROUP-SPECIFIC POLYSACCHARIDESOF GBS TO INDUCE TNF-ALPHA PRODUCTION ANDTNF-ALPHA-DEPENDENT LETHALITY IN NEONATALRATS. THE CYTOKINE WAS DETECTED IN PLASMASAMPLES BY THE L929 CYTOTOXICITY ASSAY.INTRACARDIAC INJECTIONS OF EITHERPOLYSACCHARIDE INDUCED DOSE-DEPENDENT,TRANSIENT ELEVATIONS IN PLASMA TNF-ALPHALEVELS THAT RETURNED TO BASELINE VALUESAFTER 5 H. THE GROUP-SPECIFIC ANTIGEN INDUCEDSIGNIFICANTLY HIGHER MEAN PEAK TNF-ALPHALEVELS THAN THE TYPE III ANTIGEN (125 +/- 47VERSUS 44 +/- 15 U/ML WITH 70 MG/KG OF BODYWEIGHT). GLYCOGEN (70 MG/KG), USED AS ANEGATIVE CONTROL, DID NOT INDUCE TNF-ALPHA.THE LIPOPOLYSACCHARIDE-NEUTRALIZING AGENTPOLYMYXIN B DID NOT DECREASE TNF-ALPHALEVELS INDUCED BY EITHER POLYSACCHARIDE,RULING OUT CONTAMINATION WITH ENDOTOXIN AS APOSSIBLE CAUSE OF TNF-ALPHA INDUCTION. FIFTYPERCENT LETHAL DOSES OF THE TYPE III ANDGROUP-SPECIFIC ANTIGENS GIVEN ASINTRACARDIAC INJECTIONS WERE 105 AND 16MG/KG, RESPECTIVELY. SALMONELLA ENDOTOXIN,USED AS A POSITIVE CONTROL, HAD A 50% LETHALDOSE OF 0.1 MG/KG. THE LETHAL ACTIVITIES OF GBSPOLYSACCHARIDES, AS WELL AS ENDOTOXIN, WERECOMPLETELY PREVENTED BY PRETREATMENT OFNEONATAL RATS WITH THE RESPECTIVE SPECIFICANTIBODIES OR ANTI-MURINE TNF-ALPHA SERUM. TOASSESS THE RELATIVE IMPORTANCE OF THE TYPE-SPECIFIC SUBSTANCE IN TNF-ALPHA INDUCTION BYWHOLE BACTERIA, TWO UNRELATED GBSTRANSPOSON MUTANTS DEVOID OF ONLY THE TYPE-SPECIFIC CAPSULAR POLYSACCHARIDE (COH1-13AND COH31-15) WERE EMPLOYED. EACH OF THEHEAT-KILLED UNENCAPSULATED MUTANTS WAS ABLETO PRODUCE PLASMA TNF-ALPHA LEVELELEVATIONS OR TNF-ALPHA-DEPENDENT LETHALITYBUT WAS SIGNIFICANTLY LESS EFFICIENT IN THESEACTIVITIES THAN THE CORRESPONDINGENCAPSULATED WILD-TYPE STRAIN. THESE DATASUGGEST THAT THE PRESENCE OF TYPE-SPECIFICMATERIAL ON GBS IS NOT NECESSARY FOR THESTIMULATION OF TNF-ALPHA PRODUCTION. TYPE IIICAPSULAR POLYSACCHARIDE, HOWEVER, CANSIGNIFICANTLY INCREASE THE ABILITY OF GBS TOINDUCE TNF-ALPHA. FURTHER STUDIES WILL BE


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NEEDED TO ASSESS THE IMPORTANCE OF TNF-ALPHA INDUCTION BY THE GROUP- AND TYPE-SPECIFIC ANTIGENS IN THE PATHOPHYSIOLOGY OFGBS DISEASE.


INFECT IMMUN. 1994 JUL;62(7):2748-53.ANNO: 1994 - ISBN:

Titolo

CROSS-TOLERANCE BETWEEN BACTERIALENDOTOXIN AND GROUP B STREPTOCOCCUS INNEONATAL RATS

Autori

MANCUSO, GIUSEPPE CUSUMANO, VITALIANO TETI,GIUSEPPE

Abstract


ANNO: 1994 - ISBN:

Titolo

CYTOKINE APPEARANCE AND EFFECTS OFANTITUMOR NECROSIS FACTOR- ALPHA ANTIBODIESIN A NEONATAL RAT MODEL OF GROUP-BSTREPTOCOCCAL INFECTION

Autori


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TETI G, MANCUSO G, TOMASELLO F.

Abstract

CYTOKINES ARE SUSPECTED OF PLAYING ANIMPORTANT ROLE IN THE PATHOPHYSIOLOGY OFSEPTIC SHOCK. THIS STUDY WAS UNDERTAKEN TODETERMINE WHETHER TUMOR NECROSIS FACTORALPHA (TNF-ALPHA) INDUCES THE PRODUCTION OFOTHER CYTOKINES AND MEDIATES MORTALITY IN ANEONATAL RAT MODEL OF SEPSIS CAUSED BYGROUP B STREPTOCOCCI (GBS). WE HAVEMEASURED TNF-ALPHA, INTERLEUKIN-1 ALPHA (IL-1ALPHA), INTERLEUKIN-6 (IL-6), AND GAMMAINTERFERON (IFN-GAMMA) LEVELS IN NEONATALRATS INFECTED WITH DIFFERENT STRAINS (H738,259, AND 90) AND DOSES (1 50% LETHAL DOSE [LD50]AND 5 90% LETHAL DOSES [LD90]) OF TYPE III GBS.TNF-ALPHA AND IL-6 WERE DETECTED BY THE L929CYTOTOXICITY AND THE B9 PROLIFERATION ASSAYS,RESPECTIVELY, IN SERIAL PLASMA SAMPLES. IL-1ALPHA AND IFN-GAMMA WERE MEASURED IN SPLEENHOMOGENATES BY ENZYME-LINKEDIMMUNOSORBENT ASSAY KITS BY USING ANTIBODIESRAISED AGAINST THE CORRESPONDING MOUSECYTOKINES. PLASMA TNF-ALPHA LEVELSSIGNIFICANTLY ROSE ABOVE BASELINE VALUESWITHIN 12 H AFTER INTRAPERITONEAL CHALLENGEWITH 5 LD90 OF GBS STRAIN H738, CORRESPONDINGTO 3 X 10(3) CFU. A MEAN PEAK TNF-ALPHACONCENTRATION OF 232 +/- 124 U/ML WAS REACHEDAT 20 H. PEAK IL-1 ALPHA AND IL-6 LEVELS OF 766 +/-404 U/G AND 1,033 +/- 520 U/ML, RESPECTIVELY, WEREREACHED AT 24 H AFTER BACTERIAL CHALLENGE.MAXIMAL SPLEEN CONCENTRATIONS OF IFN-GAMMA(449 +/- 283 U/G) WERE MEASURED AT 36 H.CONCENTRATIONS OF TNF-ALPHA, BUT NOT OTHERCYTOKINES, REMAINED SIGNIFICANTLY ELEVATED AT72 H, A TIME WHEN MORTALITY APPROACHED 100%.SIGNIFICANT CORRELATIONS WERE FOUNDBETWEEN CONCENTRATIONS OF EACH OF THECYTOKINES TESTED AND THE LOGS OF CFUCONCENTRATIONS IN THE BLOOD. IN ORDER TOASCERTAIN WHETHER TNF-ALPHA INFLUENCED THEPRODUCTION OF OTHER CYTOKINES, RAT PUPSRECEIVED TWO INJECTIONS OF ANTI-MURINE TNF-ALPHA OR NORMAL RABBIT SERUM AT 2 H BEFORE


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AND AT 26 H AFTER CHALLENGE WITH LIVE GBS.PLASMA TNF-ALPHA BIOACTIVITY WASUNDETECTABLE IN ANTI-TNF-ALPHA-TREATEDANIMALS, WHILE IL-6 AND IFN-GAMMA, BUT NOT IL-1ALPHA, LEVELS WERE SIGNIFICANTLY REDUCED,COMPARED WITH NORMAL SERUM CONTROLS. RATPUPS PRETREATED WITH ANTI-TNF-ALPHA SERUMAND INFECTED WITH 1 AND 5 LD90 OF STRAINS H738AND 259 SHOWED ENHANCED EARLY (48 TO 72 H)SURVIVAL. HOWEVER, BY 96 H THIS PROTECTIONWAS NO LONGER APPARENT.


INFECT IMMUN. 1993 JAN;61(1):227-35.ANNO: 1993 - ISBN:

Titolo

DETECTION OF GROUP-B STREPTOCOCCI BY DIRECTNITROUS-ACID EXTRACTION OF VAGINAL SPECIMENSAND LATEX AGGLUTINATION

Autori

TETI, GIUSEPPE MANCUSO, GIUSEPPE

Abstract


ANNO: 1993 - ISBN:

Titolo

INDUCTION OF TUMOR-NECROSIS-FACTOR-ALPHA BYLEISHMANIA-INFANTUM IN MURINE MACROPHAGES


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FROM DIFFERENT INBRED MICE STRAINS

Autori

CHIOFALO MS, DELFINO D, MANCUSO G, LA TASSA E,MASTROENI P, IANNELLO D.

Abstract

THE PRESENT STUDY WAS UNDERTAKEN TODETERMINE WHETHER THE VISCEROTROPICSPECIES, LEISHMANIA INFANTUM, ENDEMIC IN ITALY,COULD INDUCE TUMOR NECROSIS FACTOR ALPHA(TNF ALPHA) IN MURINE MACROPHAGES.GENETICALLY SUSCEPTIBLE (LSHS) AND RESISTANT(LSHR) MICE WERE USED IN THE ATTEMPT TOCORRELATE TNF ALPHA PRODUCTION WITH THEABILITY TO CONTROL PARASITE GROWTH ANDREPLICATION. RESIDENT PERITONEALMACROPHAGES OF C3H/HEN, DBA/2, CBA (LSHR),C57BL/10 AND BALB/C (LSHS) MICE WERE INFECTEDIN VITRO WITH PROMASTIGOTES AT A PARASITE TOCELL RATIO OF 8:1. NO SIGNIFICANT DIFFERENCES INTHE PERCENTAGES OF INFECTED PERITONEALCELLS OF LSHS VERSUS LSHR MICE WEREOBSERVED UNTIL 72 H OF IN VITRO CULTURE. ON THECONTRARY, KUPFFER CELLS FROM LSHR MICEINHIBITED LEISHMANIA REPLICATION. PERITONEALMACROPHAGES OF RESISTANT MICE PRODUCEDSIGNIFICANTLY HIGHER AMOUNTS OF TNF ALPHA ASCOMPARED TO SUSCEPTIBLE MICE. TNF ALPHAPRODUCTION OF BOTH RESISTANT ANDSUSCEPTIBLE MICE PEAKED AT ABOUT 5 H AFTERTHE CHALLENGE WITH THE PARASITE. NO TNF ALPHAWAS FOUND IN SUPERNATANTS OF INFECTEDKUPFFER CELLS FROM ALL THE STRAINS TESTED.THE ABILITY OF MACROPHAGES FROM SUSCEPTIBLEOR RESISTANT MICE STRAINS TO PRODUCE TNFALPHA AFTER CHALLENGE WITH LEISHMANIAINFANTUM DOES NOT SEEM RELATED TO THEIRCAPACITY TO CONTROL PARASITE REPLICATION INVITRO.



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MICROB PATHOG. 1992 JAN;12(1):9-17.ANNO: 1992 - ISBN:

Titolo

SYNTHESIS AND IMMUNOLOGICAL PROPERTIES OFAN O-STEAROYL POLYSACCHARIDE FROM GROUP-BSTREPTOCOCCI

Autori

TETI G., TOMASELLO F, MANCUSO G

Abstract


JOURNAL OF IMMUNOLOGICAL RESEARCH, VOL. 4, P.67-72, ISSN: 1120-3765ANNO: 1992 - ISBN:

Titolo

PRODUCTION OF TUMOR-NECROSIS-FACTOR-ALPHAAND INTERLEUKIN-6 IN MICE INFECTED WITHGROUP-B STREPTOCOCCI

Autori

TETI G, MANCUSO G, TOMASELLO F, CHIOFALO MS.

Abstract

GROUP B STREPTOCOCCI (GBS) ARE A LEADINGCAUSE OF SEPSIS AND MENINGITIS IN NEONATES.SINCE CYTOKINES ARE THOUGHT TO PLAY ANIMPORTANT ROLE IN SEPTIC SHOCK, WE HAVE


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STUDIED SERUM LEVELS OF TUMOR NECROSISFACTOR-ALPHA (TNF ALPHA) AND INTERLEUKIN-6(IL-6) IN BALB/C MICE INFECTED WITH TYPE III GBS.TNF ALPHA AND IL-6 WERE DETECTED BY THE L929CYTOTOXICITY AND THE B9 PROLIFERATION ASSAYS,RESPECTIVELY, IN SERIAL SERUM SAMPLESOBTAINED AFTER INFECTION. AFTER I.P. CHALLENGEWITH AN LD50, SERUM TNF ALPHA ROSE ABOVEBASELINE VALUES AS EARLY AS 3 HR, PEAKED AT 7HR, AND RETURNED TO BASELINE VALUES AT 20 HR.IL-6 SERUM LEVELS ROSE CONCOMITANTLY WITH TNFALPHA, PEAKING 8 HR AFTER CHALLENGE. NO SERUMTNF ALPHA ACTIVITY WAS DETECTED IN THE COURSEOF SUBLETHAL INFECTIONS. HOWEVER, ATRANSIENT RISE IN TNF ALPHA LEVELS WASOBSERVED AFTER I.V. INOCULATION OF HIGHNUMBERS (GREATER THAN OR EQUAL TO 1 X 10(8) OFHEAT-KILLED GBS. WHEN GROUPS OF MICE WEREINJECTED I.V. WITH A SINGLE DOSE OF ANTI-TNFALPHA RABBIT SERUM 2 HR BEFORE CHALLENGEWITH AN LD90 OR LD30, NO EFFECT WAS NOTED INTERMS OF SURVIVAL, ALTHOUGH THE SERUM TNFALPHA PEAK WAS COMPLETELY ABROGATED. SERUMTNF ALPHA DOES NOT SEEM TO PLAY ANOBLIGATORY ROLE IN GBS-INDUCED LETHALITY OFADULT MICE. HOWEVER, FURTHER STUDIES ARENEEDED TO ASSESS BETTER THE ROLE OF THISCYTOKINE IN THE PATHOGENESIS OF GBS SEPSIS.


CIRC SHOCK. 1992 OCT;38(2):138-44.ANNO: 1992 - ISBN:

Titolo

SPECIFICITY AND PROTECTIVE ACTIVITY OF MURINEMONOCLONAL- ANTIBODIES DIRECTED AGAINST THECAPSULAR POLYSACCHARIDE OF TYPE-III GROUP-BSTREPTOCOCCI

Autori

TETI G., CALAPAI M, CALOGERO G, TOMASELLO F,


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MANCUSO G, GALLI A, RIGGIO G

Abstract

WE HAVE OBTAINED 41 MONOCLONAL ANTIBODIESDIRECTED AGAINST TYPE III GROUP BSTREPTOCOCCI BY IMMUNIZING BALB/C MICE WITHFORMALIN-KILLED BACTERIA. ALL OF THESEANTIBODIES REACTED WITH PURIFIED TYPE-SPECIFIC CARBOHYDRATE BY ENZYME-LINKEDIMMUNOSORBENT ASSAY AND IMMUNOPRECIPITATIONTESTS. THE EPITOPE RECOGNIZED BY ALL OF THESEANTIBODIES WAS ASSOCIATED WITH TERMINALSIALIC ACID RESIDUES, AS INDICATED BYABROGATION OF IMMUNE REACTIONS BY TREATMENTOF THE TYPE-SPECIFIC CARBOHYDRATE WITHNEURAMINIDASE. TWO PURIFIED MONOCLONALANTIBODIES (THE IGM P9D8 AND THE IGG3 P4F12)WERE FURTHER CHARACTERIZED FOR THEIRPROTECTIVE ACTIVITY IN A NEONATAL RAT MODELOF INFECTION. P9D8 AND P4F12 ANTIBODIES WERESIGNIFICANTLY PROTECTIVE WHEN ADMINISTEREDIN A DOSE OF 0.5 AND 2.5 MG/KG, RESPECTIVELY, ATTHE SAME TIME AS 3 X 10(5) COLONY FORMING UNITSOF TYPE III STREPTOCOCCI. PROTECTION WAS STILLOBSERVED WHEN THE ANTIBODIES WERE GIVEN UPTO 9 H AFTER CHALLENGE. NO PROTECTION WASAFFORDED AGAINST INFECTIONS WITH TYPE IA/CAND II STREPTOCOCCI. SIMILARLY, BOTH ANTIBODIESEFFECTIVELY OPSONIZED TYPE III, BUT NOT IA, IB ORII BACTERIA, IN AN IN VITRO ASSAY. THESE ANDSIMILAR, PREVIOUSLY DESCRIBED, MONOCLONALANTIBODIES MAY BE USEFUL, POSSIBLY AFTER"HUMANIZATION" BY GENETIC ENGINEERING, FOR THETHERAPY OF NEONATAL GROUP B STREPTOCOCCALINFECTIONS.


HYBRIDOMA, VOL. 11, P. 13-22, ISSN: 0272-457XANNO: 1992 - ISBN:

Titolo


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MODULATION OF THE INTRINSIC ANTIVIRAL ACTIVITYBY ESCHERICHIA COLI ENDOTOXIN IN MACROPHAGESFROM PATIENTS WITH NEOPLASIA.

Autori

MERENDINO RA, ARENA A, MANCUSO G, ZUMMO S,CHILLEMI S, MESITI M, BONINA L.

Abstract

MACROPHAGES FROM PATIENTS WITH BREASTCANCER SHOWED AN IMPAIRMENT OF THEIRANTIVIRAL ACTIVITY. THE CAPABILITY TO HINDERHERPES SIMPLEX VIRUS TYPE 2 REPLICATION OFMACROPHAGES FROM HEALTHY DONORS AND FROMPATIENTS WITH BREAST CANCER WAS COMPARED TOTHE IN-VITRO TREATMENT WITH ESCHERICHIA COLILIPOPOLYSACCHARIDE (LPS). THE LPS SHOWED ADOSE-DEPENDENT EFFECT ON THE DIFFERENTMACROPHAGE POPULATIONS STUDIED.NEVERTHELESS, MACROPHAGES FROM HEALTHYDONORS APPEARED TO BE MORE SENSITIVE TO LPSIN COMPARISON WITH MACROPHAGES FROM THEPATIENTS UNDER OUR OBSERVATION. ON THESECELLS LPS TREATMENT WAS NOT ABLE TO MODIFYTHE ANTIVIRAL PROPERTY, WHEN THESEMACROPHAGES WERE DIFFERENTIATED INAUTOLOGOUS SERUM.


J CHEMOTHER. 1991 FEB;3(1):16-22.ANNO: 1991 - ISBN:

Titolo

ROLE OF SALMONELLA-ENTERITIDISLIPOPOLYSACCHARIDE ON ANTI-HSV ACTIVITY OFMACROPHAGES FROM DIFFERENT ANATOMICALSITES


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Autori

ARENA A, MERENDINO RA, MASTROENI P, MANCUSOG, COSTA GB, BONINA L.

Abstract

IT IS GENERALLY AGREED THAT ENDOTOXINS FROMGRAM-NEGATIVE BACTERIA PLAY A MODULATORYROLE ON SEVERAL MACROPHAGE FUNCTIONS. THEINTRINSIC ACTIVITY VERSUS HERPES SIMPLEX VIRUSTYPE 1 AND TYPE 2 OF KUPFFER CELLS, PERITONEALAND ALVEOLAR MACROPHAGES, HARVESTED FROMNORMAL AND TUMOUR-BEARING RATS, WASEVALUATED. MOREOVER, THE EFFECTS OFDIFFERENT INTRAVENOUS TREATMENTS WITH S.ENTERITIDIS ENDOTOXIN WERE INVESTIGATED. THEANTIVIRAL ACTIVITY OF PERITONEAL, ALVEOLARMACROPHAGES AND KUPFFER CELLS FROMTUMOUR-BEARING RATS IS DEFINITELY IMPAIRED BUTIT APPEARS TO BE POSITIVELY MODULATED BY IN-VIVO ADMINISTRATION OF S. ENTERITIDISLIPOPOLYSACCHARIDE (LPS).


INT J TISSUE REACT. 1989;11(4):169-73.ANNO: 1989 - ISBN:

Titolo

ENHANCEMENT OF RIBAVIRIN EFFICACY VERSUSHSV-SYSTEMIC INFECTION BY P40 FRACTIONTREATMENT.

Autori

ARENA ADRIANA, D. IANNELLO, M.C. LIBERTO, G.MANCUSO, R. MERENDINO, PI. MASTROENI, L. BONINA.


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Abstract


INTERNATIONAL JOURNAL OF IMMUNOTHERAPY, VOL.IV, P. 151-156, ISSN: 0255-9625ANNO: 1988 - ISBN:

Titolo

COMBINED EFFECTS OF RIBAVIRIN ANDMONONUCLEAR PHAGOCYTIC CELLS ON VIRUSREPLICATION

Autori

ARENA A., MERENDINO R.A., LIBERTO M.C., MANCUSOG., BONINA L., MASTROENI P

Abstract


INTERNATIONAL JOURNAL OF IMMUNOTHERAPY, VOL.3, P. 313-317, ISSN: 0255-9625ANNO: 1987 - ISBN:

CAPACITÀ ECOMPETENZE

PERSONALI

LE PRINCIPALI COMPETENZE PERSONALI ACQUISITENELL’ATTIVITÀ DIAGNOSTICA SVOLTA SIA NELLABORATORIO DI MICOLOGIA E MICOBATTERIOLOGIACHE PRESSO IL LABORATORIO CENTRALIZZATO DIPATOLOGIA CLINICA DELLA AOU "G. MARTINO" DI


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MESSINA E NELL’ATTIVITÀ DI RICERCA SVOLTA NEILABORATORI DI RICERCA DEL DIPARTIMENTO DIPATOLOGIA E MICROBIOLOGIA SPERIMENTALE DELLAFACOLTÀ DI MEDICINA E CHIRURGIADELL'UNIVERSITÀ DEGLI STUDI DI MESSINARIGUARDANO L’UTILIZZO DELLE SEGUENTIMETODICHE: 1-DOSAGGIO IMMUNOLOGICO IFN-Γ PERLA RILEVAZIONE DI TUBEROCLOSI LATENTE (QTF-TBGOLD) 2-GENE PROBE PER RILEVAMENTO DI M.TUBERCOLOSIS COMPLEX DA CAMPIONE MEDIANTEAMPLIFICAZIONE 3-GENE PROBE PERIDENTIFICAZIONE DA COLTURA MEDIANTE UTILIZZODI BIOPROBES SPECIFICHE PER M. TUBERCOLOSISCOMPLEX E MICOBATTERI ATIPICI 4-ESAMECOLTURALE ED ANTIBIOGRAMMA M. TUBERCOLOSISMEDIANTE METODO FLUORIMETRICO; ESAMECOLTURALE ED ANTIBIOGRAMMA MICOBATTERIATIPICI A RAPIDA E LENTA CRESCITA DA PAZIENTIAFFETTI DA FIBROSI CISTICA 5-ESAME COLTURALEMICOBATTERI SU TERRENO SOLIDO6-OSSERVAZIONE MICROSCOPICA MICOBATTERIMEDIANTE COLORAZIONE 8-IDENTICAZIONE MICETIDA COLTURA MEDIANTE TESTS BIOCHIMICI9-ANTIMICOGRAMMI 10-RILEVAZIONE ANTIGENEMIAMICETI MEDIANTE REAZIONI DI AGGLUTINAZIONE 11-IDENTIFICAZIONE DI MICETI DA COLTURA MEDIANTERICERCA ACIDI NUCLEICI 12. UTILIZZO DISTRUMENTAZIONI SCIENTIFICHE PERL'ESPLETAMENTO DEL DOSAGGIO DI ANALITIRELATIVI ALLA CHIMICA CLINICA, AGLI ENZIMICARDIACI DI PERTINENZA CARDIOLOGICA ED ALLACOAGULAZIONE 13. DOSAGGIO IMMUNOENZIMATICOE BIOLOGICO DI CITOCHINE UMANE E MURINE 14.APPLICAZIONE DI TECNICHE DI COLTIVAZIONECELLULARE 14. MESSA A PUNTO DI MODELLISPERIMENTALI ANIMALI.

PRIMA LINGUA

ITALIANO

ALTRE LINGUE


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INGLESE

Capacità di lettura

ECCELLENTE

Capacità di scrittura

ECCELLENTE

Capacità di espressioneorale

BUONO

FRANCESE

Capacità di lettura

ECCELLENTE

Capacità di scrittura

BUONO

Capacità di espressioneorale

BUONO

CAPACITÀ ECOMPETENZERELAZIONALI

PRESENTA LA CAPACITÀ DI INTRATTENERE BUONIRAPPORTI INTERPERSONALI CON I COLLEGHI DI


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LAVORO MOSTRANDO INOLTRE UN BUONORIENTAMENTO NEI CONFRONTI DELL’UTENZAINTERNA ED ESTERNA ESSENDO IN GRADO DIATTUARE, OVE NECESSARIO, INIZIATIVE ATTE ADINCREMENTARE LA CAPACITÀ COMUNICATIVA. E’DOTATO DI UNA BUONA VERSATILITÀ CHE GLICONSENTE DI SVOLGERE COMPITI DIFFERENTI ASECONDO DELLE NECESSITÀ DELL’UNITÀ OPERATIVADI APPARTENENZA E DI ADEGUARSI AI CAMBIAMENTI,ANCHE REPENTINI, NEL RISPETTO DELLE ESIGENZEAZIENDALI. QUESTE CARATTERISTICHE RELAZIONALIGLI HANNO CONSENTITO DI PERSEGUIRE GLIOBIETTIVI COMUNI IN COLLABORAZIONE CON GLIALTRI DIRIGENTI.


ORGANIZZATIVE

RESPONSABILE SPERIMENTALE DEI SEGUENTIPROGETTI DI RICERCA CONDOTTI INCOLLABORAZIONE CON LA DITTA NOVARTIS ANDVACCINES DIAGNOSTICS DI SIENA:1)MESSA A PUNTODI UN VACCINO SPERIMENTALE NEI CONFRONTIDELLE INFEZIONI DA S. PNEUMONIAE;2)IDENTIFICAZIONE DI ANTIGENI CANDIDATIVACCINALI NELLE INFEZIONI CAUSATE DA S. AUREUS;3) ALLESTIMENTO DI UN VACCINO INNOVATIVOCONTRO STREPTOCOCCO DI GRUPPO A; 4)STUDIODELL'ATTIVITÀ IMMUNOLOGICA DI ADIUVANTIIMPIEGATI NELL'ALLESTIMENTO DI VACCINO PER USOCLINICO. HA SVOLTO ATTIVITÀ DI "REFEREE" PER LESEGUENTI RIVISTE SCIENTIFICHE INTERNAZIONALI:J.LEUK. BIOL. E J. IMMUNOL. HA PARTECIPATO DAL2004 AI CONGRESSI NAZIONALI DELLA SOCIETÀITALIANA DI MICROBIOLOGIA IN QUALITÀ DIRELATORE. CITAZIONE IN WHO'S WHO IN THE WORLD,MARQUIS, EDITION 2009. SVOLGE ATTIVITÀ DITUTORAGGIO NELL'AMBITO DEI DOTTORATI DIRICERCA IN BIOTECNOLOGIE MICROBICHE E DELLAPROLIFERAZIONE CELLULARE (XVII°-XXVIII° CICLO) ENELL'AMBITO DELLA SCUOLA DI SPECIALIZZAZIONEIN MICROBIOLOGIA E VIROLOGIA DELL'UNIVERSITÀDEGLI STUDI AGGREGATE DI MESSINA, CATANIA EPALERMO. E' STATO TITOLARE DI FINANZIAMENTI DIRICERCA NELL'AMBITO DEI PROGETTI DI RICERCA DIATENEO (PRA) DELL'UNIVERSITÀ DEGLI STUDI DI


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MESSINA ININTERROTTAMENTE DALL'ANNO 2000 ATUTT'OGGI. HA PRESO PARTE AI SEGUENTIPROGETTI INTERNAZIONALI FINANZIATI DALLACOMUNITÀ EUROPEA IN QUALITÀ DI COMPONENTEDELL’UNITÀ OPERATIVA DIRETTA DAL PROF. G. TETI:1)FINANZIAMENTO COMUNITÀ EUROPEA PER ILPROGETTO “HOSPATH” CONTRATTO N° QLK2-CT-2000-00336; COORDINATORE EUROPEO: PROF. T.ESPEVIK (INSTITUTE FOR CANCER RESEARCH,UNIVERSITY OF TRONDHEIM, NORVEGIA); UNITÀOPERATIVA: PROF. G. TETI, DIP. PATOLOGIA EMICROBIOLOGIA SPERIMENTALE, UNIVERSITÀ DIMESSINA. 2)FINANZIAMENTO COMUNITÀ EUROPEAPER IL PROGETTO “PEPSAC-MIMIC” CONTRATTO N°QLK2-CT-1999-00854; COORDINATOREINTERNAZIONALE: DOTT. M. OGGIONI (ISTIT.MICROBIOLOGIA, UNIVERSITÀ DI SIENA); UNITÀOPERATIVA:SOTTO CONTRATTO STIPULATO CONPROF. G. TETI, DIP. PATOLOGIA E MICROBIOLOGIASPERIMENTALE, UNIVERSITÀ DI MESSINA.NELL'AMBITO DELL'ATTIVITÀ DIDATTICA SVOLGELEZIONI FRONTALI, ATTIVITÀ INTERATTIVA, SEMINARIED ESERCITAZIONI ORGANIZZANDO GRUPPI DLLAVORO FRA GLI STUDENTI DEL PROPRIO CORSO DILAUREA. E' STATO RELATORE DI NUMEROSI TESIFINALI NELL'AMBITO DEI DIVERSI CORSI DIDOTTORATO E DI SPECIALIZZAZIONE.


TECNICHE

LE PRINCIPALI COMPETENZE TECNICHE ACQUISITEED APPLICATE NEL SERVIZIO DIAGNOSTICO DIMICOLOGIA E MICOBATTERIOLOGIA DELL'AOU DIMESSINA E NEI LABORATORI DI RICERCA DELDIPARTIMENTO DI PATOLOGIA E MICROBIOLOGIASPERIMENTALE DELLA FACOLTÀ DI MEDICINA ECHIRURGIA DELL'UNIVERSITÀ DEGLI STUDI DIMESSINA RIGUARDANO LE SEGUENTI TIPOLOGIE DIATTREZZATURE SCIENTIFICHE: 1-BACTEC MGIT 960 A(MICOBATTERI) 2-BACTEC 9050 (EMOCOLTUREMICETI) 3-ANALIZZATORE DI IMMAGINI PHARMACIABIOTECH VDS 4-TERMOCICLATORE PCR5-LUMINOMETRO 6-MICROSCOPIO OTTICO,CONTRASTO DI FASE, FLUORESCENZA. CONOSCENZADEI PIÙ COMUNI SISTEMI OPERATIVI (WINDOWS XP,


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VISTA) E DI SOFTWARE APPLICATIVI ANCHE DITIPOLOGIA SPECIALISTICA (WORD, MICROSOFTEXCEL, POWER POINT, ADOBE PHOTOSHOP, PRIMEROF BIOSTATISTIC, CRICKET GRAPH).

PATENTE OPATENTI

PATENTE B


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FORMATO PER IL CURRICULUM VITAE - polime.it · 2020. 5. 25. · 2014. -docente di microbiologia...

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