Ascaris spp Antigens - m-hikari.com · The Ascaris suum cuticle similarly to other nematodes, is a...

Contemporary Engineering Sciences, Vol. 11, 2018, no. 7, 333 - 355HIKARI Ltd, www.m-hikari.com

https://doi.org/10.12988/ces.2018.8122

Ascaris spp Antigens

Omar Fernando Cuadro Mogollon

Environmental Engineer, University Corporation of Huila - CorhuilaNeiva, Republic of Colombia

Ricardo Pena Florez

Veterinary Medicine and Zootechnia, Cooperative University of ColombiaNeiva, Republic of Colombia

Arlex Rodrıguez Duran

Veterinary Medicine and Zootechnia, Cooperative University of ColombiaMedellın, Republic of Colombia

July Steffany Gonzalez Lopez

Environmental Engineer, University Corporation of Huila - CorhuilaNeiva, Republic of Colombia

Copyright c© 2018 Omar Fernando Cuadro Mogollon et al. This article is distributed

under the Creative Commons Attribution License, which permits unrestricted use, distribu-

tion, and reproduction in any medium, provided the original work is properly cited.

Abstract

A parasitic infestation is not only the fact that a multicellular organ-ism is living inside another and developing at its expense, but also it isnecessary to recognize that there are a large number of host-parasite in-teractions of intriguing complexity, which are articulated and convertedinto strategies of two sides in a continuous and interesting war. Thestudy of some soluble and surface antigens of Ascaris, being an impor-tant part of the evasion or modulation immune response strategies, itis preponderant to understand the pathogenesis particularities of theparasite and the possible use of some of these antigens as therapeu-tic targets in the control of this disease and others as asthma, whichkeeps closeness in terms of the immune mechanisms that mediate them.

334 Omar Fernando Cuadro Mogolln et al.

Therefore, this review presents some Ascaris antigens and it describesthe biological function and possible therapeutic utilities in the medicaland immunological field. The homologous immune parameters betweenallergic-type diseases such as asthma and the response stimulated byAscaris are also related and some interesting perspectives are proposedthat will serve as a platform for future research.

Keywords: Ascaris, Surface Antigens, Immunomodulators, Asthma

1 Introduction

In order to control endoparasites, they are confronted by host defences throughthe activity of multiple physical barriers, innate immunity and adaptive im-mune response [1], which seek to eradicate the disease. All the parasitic infec-tions that progress, have in common that the pathogens can evade or resist theimmune response effects of the host and in addition to survive in it for longperiods [2], articulating a wide range of host-parasite interactions. Generally,the activity of these immune defences is based on an efficient pathogens recog-nition through the surface antigens identification. Thus, the cover nature ofthe parasites and the secretion and excretion products are fundamental in theinteraction of these with the host [3].

The external cover of the parasitic worms is considerably different betweenedges, this is how the flatworms have a dynamic tegument formed by a uniquesyncytial organization, existing an anucleated surface layer, which is connectedat interval through cytoplasmic tubes or trabeculae to a nucleated lower re-gion or tegumental cell body [4][5]. This becomes an interfacial organ withadsorption, nutrition, synthesis and secretion functions of biomolecules and abidirectional flow of molecules and information between host and the parasite,which is able to react dynamically to changes in potentially damaging envi-ronmental conditions. On the other hand, the nematodes cuticle is an inertlayer of extracellular material, rich in crosslinked collagen fibers and insolubleproteins that can be relatively simple or very complex. This is synthesizedand secreted by an underlying dermis and covered by a lipophilic epicuticleand a glycocalyx exterior, derived from the products of specialized secretoryglands [6]. The two types of covers provide isolation and protection againstattack and degradation by host agents, such as digestive enzymes, detergentbile acids or components of the immune system during parasitic infection tothe host.

The Ascaris suum cuticle similarly to other nematodes, is a complex struc-ture composed mainly of extracellular proteins with trace amounts of lipidsand carbohydrates. The basic cuticular structure consists of the epicuticle, anexternal cortical region and a medial one, besides the basal layers [7]. It is

Ascaris spp antigens 335

composed of proteins as collagen, that forms the medial and basal layers, non-collagenic proteins contribute to the epicuticular and external cortical regions,as well as the non-structural proteins associated with the external surface [8].The cuticle is synthesized in each moult and the amount and type of cuticu-lar proteins can vary with the stage in which the parasite is found. Due tothe enormous versatility in the structural components synthesis of the cuti-cle, the epicuticle and the glycocalyx, Ascaris sp becomes an important agentthat generates antigens during infection and therefore the occurrence of vari-ous immune-type phenomena is likely, pathogenic and nutritional between theparasite and the host derived from the epitopes that compose it. Because of itspotential impact on protective immunity, pathogenesis and development of al-lergic diseases (e.g. asthma), the characterization of Ascaris immunogenic andallergenic components is essential [9]. Similarly, the identification of parasite-specific antigens is critical for the safe and successful vaccines development, inorder to prevent that antibodies cross-react with host proteins [10]. Thus, areview is undertaken about the main pathological implications of Ascaris andsome substances released or anchored to the surface of this parasite, whichcan be antigens or surface allergens and some of their possible biological andimmunological interactions.

2 Antigens derived from excretion / secretion

The Ascaris suum secretum consists of about 750 different molecules, it is richin peptidases, linked to the penetration and degradation of host tissues andmolecules that interact with cells and immune molecules, being responsiblefor modulating or evading the responses host immune system [11]. The se-cretion products are substances with certain biological functions. Conversely,the excretion products are unnecessary metabolic derivatives that are releasedfrom the parasite [12]. The chemical nature of both of them is varied and mayinclude different glycoproteins, proteins and smaller peptides. Additionally,non-protein components that include glycans, glycolipids and bioactive lipids,such as eicosanoid inflammatory mediators and substances whose function hasnot yet been established. The entire set of excretion/secretion proteins iden-tified by Wang [13], 24% corresponding to 38 of the proteins, have unknownfunction or homologs in other organisms and they are therefore constitutedas substances with significant biological potential in the interactions betweenAscaris and the host.

2.1 Metabolic mediators

Another important functional group of substances of Ascaris suum secretionare the metabolic mediators, which are the enzymes that participate in the


primary degradation of diverse substrates and predominate in the stages L3and L4, mainly in pulmonary, hepatic and intestinal infections. The enzymessecreted mainly are the glycosylhydrolases belonging to the 31 (GH31) family,where 16 proteins with determined function were identified [13]. Like otheranaerobic parasites, Ascaris suum uses exogenous glucose for the energy gen-eration through the glycolytic pathway [14], which incorporates external glu-cose and decomposes it with glycolytic enzymes such as maltose-glucoaminase,sucrase-isomaltase, fructose-bisphosphate-aldolase and fumarate-reductase. How-ever, while they are potentially foreign substances for the host body, sincethey do not present any type of genomic homology or in their amino acid se-quences with human molecules, the antigenic or allergenic value of any of theaforementioned enzymes has not been demonstrated [15]. On the other hand,enolases (hydrolases 2-phospho-D-glycerate) are essential glycolytic enzymesthat catalyse the interconversion of 2-phosphoglycerate and phosphoenolpyru-vate and they are excretion/secretion products of Ascaris [13]. In addition,the enolases have an antigenic importance to the point of being a potentialcandidate for the development of vaccines against Ascaris suum and it hasbeen shown to stimulate the production of cytosines belonging to a Th2-typelymphoproliferative reaction [14]. Enolases are important allergens and wereshown to induce cross-reactivity with fungal and vegetable enolase [16], andparasitic enolase is involved in the redirection of RNAt and can play an im-portant role in the proteins expression [17]. Instead, the enzymes glutathionetransferase of Ascaris (GSTA), which fulfil important biological functions ofdetoxification in the parasite, it has demonstrated its allergenic potential [9]since generally, the enzymes of the GST family of invertebrates can inducesignificant sensitization of IgE in humans [18], although there are several iso-forms that can influence their antigenic capacity and have clinical relevance aspotential vaccines, despite their allergenicity.

Endochitinases and lysozyme 2 of the GH25 family are other importantenzymes released by Ascaris summ [13], which catalyse the hydrolysis of β-1,4-N-acetyl-d-glucosamine bonds in polymers of Chitin and they are mediatorsin the hatching and shedding processes of the parasite [19][20], both of themwith cysteine proteases in nematodes (such as serine proteases, metallopro-teases and aspartic proteases) have potential roles in the old cuticle digestionand the moult activation [21]. Therefore, interest in the chitinases potential astargets for drugs or vaccines has been raised [22]. At this point, it should benoted that several known allergens are proteases, since the central proteolyticactivity endows the molecules with intrinsic allergenicity. Consequently, cys-teine protease from dust mites (Der p1), cockroach aspartate protease (Bla g2), serine protease from Aspergillus fumigatus and bacterial subtilisins are im-portant allergenic molecules [23] and it leads to suppose that Ascaris chitinasesand proteases may possess this property. On the other hand, GH25 lysozymes


are enzymes that share the ability to specifically hydrolyze the β-1,4-glycosidicbond between N-acetylmuramic acid (NAM) and Nacetylglucosamine (NAG)of the bacterial peptidoglycan. In addition to the muramidase activity, chiti-nase activity is also witnessed, probably as a result of the similarity betweenpeptidoglycan and chitin [24]. This probably involves lysozymes in the cu-ticle degradation process during moult, most of the lysozymes of the GH25family are produced by bacteria and fungi, therefore, they could be consti-tuted as foreign substances with immune stimulation capacity. It has not beenreported that any of the Endochitinases have allergenic or antigenic proper-ties in human hosts. Another group of enzymes secreted by Ascaris suumare aminopeptidases [25], it can be highlighted an aspartate protease with anoptimum pH of 3.5, a serine protease with an optimum pH of 5.6 [26], a leucine-amonopeptidase [27], as well as endopeptidases, where it has been identifiedwith properties similar to neprilysin of mammals [28][29][13]. These enzymesare capable of degrading a wide range of neuropeptides with exclusive neu-rotransmitter and neurohormon functions in the nervous system of helminths[28] and therefore, they regulate muscle relaxation of these pathogens. It hasalso been identified a metalloaminopeptidase released by Ascaris [30][25] thatcan regulate the inflammatory processes and the enzyme activity of the host.At the moment, no antigenic or allergenic properties have been reported in theendopeptidases or neprilysin secreted by A. summ.

2.2 Contractile mediators

Additionally, the contractile mediators are an essential group of substancesreleased by Ascaris summ, which are the proteins involved in the muscularmovement of the parasite. Myosin-4, paramyosin and tropomyosin are pro-teins isolated from A. summ eggs [13]. Tropomyosin is also expressed at highlevels in stage L3 of Ascaris lumbricoides, during its pulmonary stay and it iscapable of stimulating the production of important levels of human IgE [31].Thus, it has been associated with the allergic manifestations induction [32].It is convenient to highlight that tropomyosin is a recognized allergens family(AF054 AllFam, database of allergen families) composed of 47 proteins, allof them are invertebrate and rich in conserved α-helices, which is a typicalcharacteristic of substances with antigenic capacity and allergenic.

2.3 Binding proteins

Ascaris is able to synthesize and release a wide variety of other binding proteinsthat are capable of binding to different substrates. A clear example is LTBP1or latent TGF- β binding protein 1 [13], which has a double function, since itis required both for the latent TGF- β complex secretion (TGF- β + peptide


associated with latency, LAP), as well as direct the binding of latent TGF- β tothe extracellular matrix microfibrils [33]. The latent TGF- β complex has animportant immunomodulatory effect [34], also it affects the growth, differenti-ation and cells morphology. In addition, they participate in the extracellularmatrix synthesis and proteolysis regulation, they are also involved in the pro-cesses of tissue development [35][36], which denote that the LTBP1 and thelatent TGF- β produced by Ascaris are able to regulate some degrees in theimmune response and the tissues architecture during the parasitic infection.

On the other hand, Ascaris also synthesizes and releases transmembranereceptors of cell adhesion MUA-3, which are anchoring proteins belonging tofibrous organelles of muscle-cuticular insertion of helminths, similar to thehemidesmosomes of vertebrates that transmits mechanical tension of the mus-cles to the cuticle [37] and mediate their mobility. The release of transmem-brane receptors from cell adhesion MUA-3 is only recorded in larval stage L3during lung infection by Ascaris [13]. Finally, a complex protein named zon-adhesin [13], which is composed of three domains of functional proteins thatmediate cellular adhesion, it has also been identified as excretion/secretionproducts of Ascaris in the larval stage L4 [MAM meprin, A5 antigen, tyro-sine phosphatase MU receptor, von Willebrand D (VWD) and putative mucindomains] [38] which is a large protein, located in the anterior acrosome ofmammalian sperm and mediates the specific adhesion to the zona pellucida ofthe mature ovules [39]. The role of zonadresine in Ascaris is not understood,but due to its homology with different cellular receptors that participate in dif-ferent biological processes, it is a great interest subject to identify its biologicalfunction.

2.4 Immunomodulators

The ability of helminths to modulate the immune system sustains their longevityin the mammalian host [40]. Consequently, there is a great interest in under-standing the molecular basis of the helminths immunomodulation [41]. In thecase of Ascaris, it is likely that the action of suppression and activation of theimmune response components will be frequent in the substances of the psudo-coleomic fluid [68]. An evidence is the fact of the serpins release [13], which area set of proteins with multiple functions [43]. Additionally, they are involvedin a series of fundamental biological events, such as blood coagulation, fibrinol-ysis, angiogenesis, programmed cell death, cell development and inflammatoryresponse [44][45][46]. Helminth serpents also have important parasitic defencefunctions, for instance, Brugia malayi produces a serpin (Bm-SNP-2), thatspecifically inhibits cathepsin G and elastases secreted by neutrophils [47][48].A Schistosoma haematobium serpin, can be anchored in the cell membrane andhas antitrypsin activity, therefore, the complex formed between the membrane


embedded serpin and human trypsin allows the parasite to reduce immuno-genicity. Thus increasing its ability to evade the host immune defences [49].Given these cases, it is interesting to study the biological functions of Ascarisserpins and the functions they can perform during infection. On the otherhand, the most powerful Ascaris immunomodulator named PAS-1 (Suppressorprotein of Ascaris suum-1) has been identifief, which is a 200 kDa protein thatis able to regulate humoral and cellular responses by stimulating the produc-tion of INF-γ. IL-10 and TGF-β, are also able to decrease cell recruitment anddecrease the production of IL-4 and IL-5, as well as suppress the productionof anaphylactic IgE and IgG1 antibodies [42][50], therefore, they are capableof reducing allergic manifestations. The refence [51] showed that regulatoryT cells (CD4 + CD25 +) and CD8 + T cells are involved in the mechanismsby which PAS-1 influences the immune system, since when these donor cellsstimulated with PAS-1 they were adaptively transferred to mice immunizedwith OVA, the allergic inflammation induced by OVA is reduced, constitutingan important molecule of pharmacological interest.

In addition, Ascaris is able to synthesize type C lectins [13] and galectins4 and 9 [11], which suggest that parasites can use lectins that bind to theremains of carbohydrates on the host cells surface to avoid pathogen recogni-tion mechanisms in the host [52]. On the other hand, galectin-9 inhibits thedifferentiation of T cells in Th17 [53], it stimulates Th1 and Th17 apoptosisdependent on TIM-3, and it promotes the expression of Foxp3 in regulatoryT cells [54][55]. The galectin-9 administration in a murine model of allergichypersensitivity of the respiratory tract reduced airway hypersensitivity, aswell as inflammation associated with Th2, galectin-9. This also inhibits theinfiltration of Th2 cells into the respiratory tract by inhibition of the adhesionmolecule CD44 biding to hyaluronan in the MEC [56].

As Ascaris is able to modulate downwards, the immune response inten-sity can also induce its hyper-reactivity through the allergenic protein gener-ation of Ascaris suum (APAS-3), of 29 kDa [57] able to induce intense pul-monary inflammation consistent with allergic asthma related to inflammatoryeosinophilic infiltration, the anaphylactic antibodies production, the cytosinesinduction of the specialized response Th2 (IL-4, IL-5), eotaxin release andhyper-reactivity of the pathways respiratory diseases [42]. It has not beendemonstrated that APAS-3 develops any other biological function beyond theimmune response stimulation and the interesting relationship has been pro-posed in the APAS-3 vs PAS-1 circuit, such as the induction and control ofthe allergic asthma manifestation in the stage of Ascaris lung infection in an-imal models [50][42]. However, it is convenient to identify the excretion peaksof the two molecules, their dynamics and correspondence during infection inorder to clarify the biological purpose of both.

Allergenic polyproteins of nematodes (APN) are a set of immunodominant


antigens and allergens [58]. In this group are an important allergen of A. lum-bricoides and A. summ, called (Ascs-1 or ABA-1), which is a 25 kDa dimericpolyprotein in its native form, in addition it is segmented into two monomersof 10 kDa and 94 amino acids under reducing conditions. It is responsible formore than 80% of the pseudocoleomic liquid allergenicity of Ascaris suum [59],it is able to bind to retinol-like fatty acids (vitamin A) and probably mediatesthe transport of these sensitive and insoluble compounds between tissues andworms [60]. As nematodes cannot synthesize these lipids, such proteins can becrucial for the nutrients extraction from their hosts. Another hypothesis thatgains strength proposes that the binding propensities of APNs to small lipidsand eicosanoids are very important in the local and even systemic regulationof the inflammatory process, the immune response and in tissue differentiationand repair [58]. An interesting ABA-1 feature is that only a subset of infectedhumans reacts immunologically to this [61][62] and in the case of individualsinfected with A. lumbricoides, no data Epidemiological studies that supportIgE antibody responses (allergic type) are associated with the development ofnatural resistance to infection [62][63].

3 Structural Antigens

To complete the extensive repertoire review of Ascaris external antigens, it isconvenient to stop now at the bound or constitutive substances of the parasitecuticle, which perform a variety of biological functions of interaction with thehost. The parasitic nematodes cuticle is composed of structural and extracel-lular proteins. More than 90% of these proteins are collagen molecules locatedin the basal layer and the middle layers of the cuticle. The outermost layersof the cuticle (the epicuticle), is composed of non-collagenous proteins, whichrepresent the structural surface of the nematodes, in Ascaris these proteinshave been called ”cuticlins” [64]. One of the main constitutive and highlycross-linked and insoluble proteins is cuticlin-1, which is a potent inducer ofantibody production [65] and probably it has to be continuously renewed. It isfound in pseudocolemic fluid and its genes increase its expression before eachmoult [66]. Cuticular collagen 12 and 13 are the essential components of theAscaris envelope [13]. These two components are the collagen family allergens.In addition, it should be mentioned that Ascaris lumbricoides uses molecularmimicry as a strategy to evade the immune response. Therefore, this is capableof absorbing and fixing on its cuticle surface the antigenic determinant of thelower blood group P1 to minimize the disparity in the antigens expression andconsequently, to reduce immunogenicity [1].

Some nematode-specific antigens of Ascaris have been identified with broadimmunogenic power. As37 pertains to this group, which is a 37 kDa protein,belonging to the immunoglobulin superfamily and with a genomic homologue


in C. elegans. This is generally located in the lateral portions of the view, onmuscle cells and in the hypodermis [67]. Another nematode-specific antigenof Ascaris is As24, which is a protein composed of 147 amino acids and it hasmore than 50% protein homology in filarial cells, but not with other knownproteins. Immunohistochemically studies showed that As24 is an endogenousprotein located in the embryonated eggs, inside the uterus and the intestineepithelium, muscular tissues and in the hypodermis of Ascaris suum. As24was also detected in the pseudocoleomic fluid [68]. Another protein recog-nized as Ascaris antigen is As16 (MW = 16 kDa) that has no similarity atthe amino acid level with any of the mammalian proteins, but it has somegenomic similarity to Caenorhabditis elegans. As16 is located in the adultworm intestine, the hypodermis and the cuticle. Furthermore, As16 has beendetected in the psudocoleomic fluid [10] and it has been shown that immu-nization with As16, together with the cholera toxin is capable of generatinga mixed protective immune response (Th1 / Th2) in pigs [69]. Finally, it isimportant to mention As14, as the first antigen capable of inducing protectionagainst Ascaris, a ubiquitous 14 kDa protein that is expressed on the parasitesurface in all larval stages and it is released by adult larvae [70]. Moreover,it is able to induce a specific IgE antibody response in rats [71]. Generally, ithas been shown that immunization with the antigens As37, As24, As16 andAs14, independently and in the presence of appropriate immunological adju-vants, induces the important and continuous production of IgG1, IgG2a, IgEand IgA in different animal models and it could induce a significant level ofprotection against infection with Ascaris suum and A. lumbricoides.

4 Reaction to Ascaris infection

The infection by Ascaris is transmitted when eggs of the parasite are consumed.After its intestinal hatching, the larvae penetrate the intestinal mucosa andcan migrate to the liver, inducing the granulomas formation, extensive inflam-mation and tissue damage [72]. Later the larvae migrate to the lungs, wherethey induce the damage formation to the respiratory tract with inflammatoryinfiltrate and perialveolar eosinophilia [73]. Finally, they migrate through theesophagus back to the intestine to reproduce and release eggs. Resistance tohelminth infection tends to be associated with the specialized Th2 response.However, the precise underlying immunological mechanisms that lead to theexpulsion of Ascaris are still being defined [74][75]. It is mainly due to thecapacity of migration and establishment in different organs during infection,added to the wide range of substances released or present on the Ascaris surface[76], and their variation in each stage, as well as the effect of various factorsthat contribute to the susceptibility intraspecific variation to infection. It isnot inappropriate to assume that in each moment, there are important varia-


tions in the reactions that the host presents to Ascaris and that the immunepatterns response vary among patients.

Several studies have been carried out around the cellular patterns and hu-moral response in humans [77] and in various animal models against differentAscaris specific antigens or the parasite, before and after chemotherapy [74].Research have shown that antibodies of all isotypes (IgM, IgG, IgA and IgE)are induced during human infections with A. lumbricoides [77] with high cir-culating levels of IgE, above 10,000 IU / ml [78] as a result of the mitogeniceffects and the various allergenic molecules (GSTA, Tropomyosin, ABA-1 andAs14) released by the parasite [79]. These allergens are also associated withincreased production of IL-4 [77] and IL-5, hyper-reactive pulmonary inflam-mation consistent with allergic asthma [42][59]. In general, it can be affirmedthat the immune response to this helminth shares mechanisms with the aller-gic reaction and it presents evolutionary and clinical links [9]. Therefore, thisparasitic infection has been associated with an increase in allergy probably dueto the cross-reactivity between the worms protein (for example, tropomyosins)and very similar molecules in dust mites and insects [75]. Likewise, it has beenshown that in some circumstances helminth infection can increase the preva-lence of atopic disease and asthma [80][81], especially in relation to Ascarislumbricoides [82]. Paradoxically, the global increase in allergy, especially inurban areas [75] has led researchers to propose a modified hygiene hypothesisin which the decrease in helminth infections is associated with an increase ofallergic diseases [83]. Several revisions show that communities with helminthinfections have reduced allergy rates [84][85]. Based on these findings, it isproposed that active suppression of Th2 responses, mediated the activity ofmolecules such as PAS-1, together with the probable function of other specificcomponents of Ascaris such as serpins or LTBP-1, they have an importanteffect in the regulation of concurrent allergic responses [86].

Another aspect that is equally interesting in the studies carried out aroundthe response to Ascaris infections is the fact of the negative correlation be-tween the amounts of IgE synthesized by the host and the susceptibility toreinfection by A. lumbricoides [87]. There is also a greater susceptibility todevelop ascariasis in individuals with a weak Th2 type response [88], whichindicates that individuals with high amounts of IgE and a polarized Th2 re-sponse have natural immunity to infections by A. lumbricoides [75]. However,these individuals are more predisposed to develop allergic episodes, atopy andpulmonary manifestations [89]. While the increase in the amounts of IgM andIgA has been related to the verme expulsion [90], added to a reaction of mainlyinflammatory type intestinal characterized by the levels increase of C-reactiveprotein, ferritin and the cationic protein of eosinophils [62], as well as signif-icant increases in IgG and IgG4 [91]. This would show that in the Ascariselimination, different effector mechanisms are immersed, such as the Th2 re-


sponse that could be highly effective in their control, likewise, the developmentof inflammatory episodes denotes the development of possible mechanisms thatthe parasite and the host expose to control and counteract this reaction. Thus,it could be involved in the reduction of allergic manifestations [92] such as thestimulation in the generation of INF-γ, IL-10 and TGF-β and the activationof Treg.

Due to various factors of variation of Ascaris cited above, which can stimu-late various alternatives of cellular and humoral reaction in each microenviron-ments of parasitic development together with an important antigenic variationand the inductive biological interactions of atopy or inmnunomodulation, ascenario of multiple possibilities in which it is very complex to establish pat-terns of immune reaction. Therefore, it has recently been proposed that thesedifferences could be linked to the genetic variations of the hosts, which isconsistent with the finding of a strong genetic component in Epidemiologicalsusceptibility studies to these parasites in individuals with a single pedigree[93]. Similarly, the study of the genetic regulation of the Ascaris mechanismsresponse, helps to understand both the resistance to parasitic infections, as thepotential links with the pathogen of allergic diseases [94]. Hence, it has beenshown that Ascaris susceptibility is polygenic [95] and consists of gene varia-tions of the main histocompatibility complex (CPH) as a whole [96][97] andgenes that are not found in this group [98]. Likewise, lucus have been identifiedon chromosomes 1, 13 and probably 8, with regions responsible for susceptibil-ity to infections [99] and it has been established that the TNFSF13B gene (alsoknown as BlyS) is involved in the determination of susceptibility and resistanceto A. lumbricoides infections as well as the 13q33 region, which was confirmedas a QTL for susceptibility to this parasite, although the underlying genes arestill unknown [100]. Finally, it must be mentioned that the results obtainedby Acevedo [95][101] suggest that the genes that protect against parasites in-fections may be different from those that predispose to asthma and atopy, afact that further stimulates research around of the infection by Ascaris, since itoffers an intriguing pathological model with many variables of immunologicalrepercussion, which constitute pieces of an interesting and elaborated puzzleto be assembled [102].

Conflict of interests. The authors declare that there is no conflict ofinterests regarding the publication of this paper.

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Received: February 15, 2018; Published: March 9, 2018

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