Leishmania Lifecycle
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Transcript of Leishmania Lifecycle
Serum Lipid Profile, Apolipoprotein E Genotype and Visceral
Leishmaniasis Infection in a Northeastern Brazilian Population
Adam P. Simons1, Gloria R. Monteiro2, Nubia N. Pontes2, Taysa M. Feitosa2, Upasna Gaur3, Richard D. Pearson4, Mary E. Wilson3, Selma M. Jeronimo2
1.University of California-Davis, Sacramento, CA, 2.Federal University of Rio Grande do Norte, Natal, Brazil, 3.University of Iowa, Iowa City, IA, 4.University
of Virginia, Charlottesville, VA
Leishmania Lifecycle
Phenotypes:1. No Current Infection (N)
-Antibody Neg.2. Acute Illness (VL)3. Asymptomatic Infection (DTH+)
-Antibody +/-
?
Environmental and Host Factors Determine Response to Infection
**Wiki commons
Cholesterol Augments Leishmania Infectivity
Rodriguez, Gaur, Wilson 2006
Cohort of families in VL endemic Area in Natal, Brazil
Family Pairs Number of PairsSibling-Sibling 692
Parent-Offspring 892Grandparent-Grandchild
268
Avuncular 414Cousin 249
Serum Lipids by Phenotype
Cholesterol Level by Phenotype vs. Age
Acute VL Effects:
• ↓ TC, HDL• ↓ ApoA, ApoB, ApoC
• ↑ TG • ↑ ApoE
Barral et al (1986)Bekaert et al (1992)Nieto (1992)
InflammationDyslipidemia
Parasitic Infection (leptospirosis)
• ↓ Total Cholesterol, HDL
• ↑ TG
Bacterial infections:• ↓ Total Cholesterol,
HDL
TNFa↑ Hepatic TG
↓ Lipoprotein Lipase
Grunfeld et al 1991
IL-6↑ LDL Rec. Expression
Liberopoulous et al 2004
ApoE
Dijk et al 1999
ApoE Genotype and Leishmaniasis?
• 109 families in Natal
• Linkage Analysis– Chr 9 (VL)– Chr 15 (DTH+)– Chr 19 (DTH+)
Source: Jeronimo et al 2007
Apolipoprotein E
Jerónimo Genome-Wide Scan 2007
ApoE Genotype Founders
Genotype
Counts Percent
E2/E3 1 2.7
E2/E4 1 2.7
E3/E3 22 59.5
E3/E4 13 35.1
E4/E4 0 0.0
Allele Counts
E2 2 2.7
E3 58 78.4
E4 14 18.9
VL FAMILIES
Genotype Counts Percent
E2/E3 2 11.8
E2/E4 0 0.0
E3/E3 10 58.8
E3/E4 5 29.4
E4/E4 0 0.0
Allele Counts
E2 2 5.9
E3 27 79.4
E4 5 14.7
CONTROL FAMILIES
Selective Pressure of ApoE
Allele % Genotype %
E2 8.3 2/2 1.4
E3 77.1 2/3 11.1
E4 14.6 3/3 58.3
2/4 2.8
3/4 26.4
4/4 0
n=72 children in Ceara
Oriá et al (2005) Wiki commons
Future Directions
• Large-power study of ApoE genotype
• Lipid metabolic pathways in VL recovery– LXR, PPAR, Cholesterol Biosynthesis
pathway gene expression across disease process.
Acknowledgments
• Mary E. Wilson, University of Iowa• Richard D. Pearson, University of Virginia• Noah Craft, University of California• Edgar Carvalho, UFBA• Cristina Otonis, UFRN• Gloria Monteiro, UFRN• Upasna Gaur, University of Iowa• Selma Jerónimo, UFRN
NIH, CNPq and UC Davis for financial support