Genetic Factors Involved in Human Susceptibility to Infection by Schistosomiasis

Abstract

Three hundred million individuals are at risk of infection by schistosomes, which cause severe kidney and liver disease, and 280 000 deaths annually. Infection levels are mainly under the control of a major locus, SM1 (Schistosoma mansoni 1), mapped in 5q31q33 region. An association between the rs1800925 polymorphism in the IL13 promoter and infection levels was detected. Subjects bearing the rs1800925T/T genotype were much less infected than individuals with other genotypes. We went on to investigate whether other polymorphisms in genes involved in the TH2 cytokine immune response could affect susceptibility to schistosome infection. An association between STAT6 rs324013 polymorphism and infection levels was also found. These two polymorphisms which have an additive effect were not strongly correlated with any other tested markers surrounding the two genes. Moreover, these polymorphisms affect transcription factor binding to the promoter regions. These results are consistent with the TH2 cytokine pathway enhancing resistance to schistosome infection.

Key concepts:

  • IL13 gene is associated to the control of infection levels in schistosomiasis.

  • STAT6 gene is associated to the control of infection levels in schistosomiasis.

  • IL13 and STAT6 polymorphisms have synergic effect.

Keywords: schistosomiasis; infection; IL13; STAT6; gene; parasitic

Figure 1.

Parasitic cycle for S. haematobium. Infection occurs when cercariae penetrate the skin (1). It loses its tail becoming a schistosomulae (2) which moves to the veins. Adults mature in the veins surrounding the intestines or bladder, depending on the species. Schistosoma haematobium matures in veins around the bladder whereas S. mansoni and S. japonicum mature in veins around the intestines (3). Females release eggs which move from the veins to the lumen of the intestine (S. mansoni and S. japonicum) or the bladder (S. haematobium). The eggs are then passed from the body in the feces or urine (4). They hatch in fresh water and release motile larvae called miracidium (5). The miracidium infect the intermediate host (6) and multiplie asexually inside it. After 4–6 weeks, a cercariae emerge (7).

Figure 2.

Results of the linkage analysis that maps the SM1 locus into the 5q31–q33 region. In this figure are also indicated the main putative candidate genes that may be involved in the control of infection levels in schistosomiasis.

Figure 3.

Multiple roles of the IL‐13 in the protection against infection by Schistosoma. aaM, alternatively activated macrophage and caM, classically activated macrophage.

Figure 4.

Subjects carrying the genotypes rs1800925C/C and rs324013C/T have higher levels of infection than subjects carrying the other genotypes. This effect was visible on the whole population, on male and on Boul village (that included the most infected subjects).

Figure 5.

Different roles of STAT6 in the protection against infection by Schistosoma and in the regulation of the gene expression in the TH2 locus.

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Arnaud V, Li J, Wang Y et al. (2008) Regulatory role of interleukin‐10 and interferon‐gamma in severe hepatic central and peripheral fibrosis in humans infected with Schistosoma japonicum. Journal of Infectious Disease 198: 418–426.

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Rodrigues V Jr, Piper K, Couissinier‐Paris P et al. (1999) Genetic control of schistosome infections by the SM1 locus of the 5q31‐q33 region is linked to differentiation of type 2 helper T lymphocytes. Infection and Immunity 67: 4689–4692.

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Isnard, Amandine, He, Hongbin, Kouriba, Bourema, and Chevillard, Christophe(Mar 2010) Genetic Factors Involved in Human Susceptibility to Infection by Schistosomiasis. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0022394]