Recent Advances in the Characterization of Genetic Factors Involved in Human Susceptibility to Infection by Schistosomiasis

Abstract

Human resistance to infection by schistosomes is associated to a strong Th2 immune. However a persistent Th2 response can cause severe kidney and liver disease in human. In this review, we mainly focused on the control of infection levels caused by schistosomes. Several experimental models allowed us to better understand the immunological mechanisms of the host against schistosome infection. High IgE and eosinophil levels are associated with resistance to infection by schistosomes and this effect is counterbalanced by IgG4. IgE and eosinophils are highly dependent on IL-4, IL-13, and Il-5, which are three main Th2 cytokines. We also examined the genetic factors involved in human susceptibility to infection by schistosomiasis. Infection levels are mainly regulated by a major locus SM1, in 5q31-q33 region, which contains the genes encoding for the IL-4, IL-13, and Il-5 cytokines. An association between an IL13 polymorphism, rs1800925, and infection levels has been shown. This polymorphism synergistically acts with another polymorphism (rs324013) in the STAT6 gene, encoding for the signal transducer of the IL13 pathway. This pathway has also been involved in atopic disorders. As helminthiasis, atopy is the result of aberrant Th2 cytokine response to allergens, with an increased production of IL-4, IL-13, Il-9 and Il-5, with high amounts of allergen-specific and total IgE and eosinophilia. However, the Th2 immune response is protective in helminthiasis but aggravating in atopic disorders. Several studies reported interplay between helminthic infections and allergic reactions. The different results are discussed here.

Human Schistosomiasis

“…On the other hand, helper T lymphocyte-2 (TH2) cytokines have been firmly associated with resistance to schistosomal infection in many animal models as well as in humans (Isnard and Chevillard, 2008). The main players are: (1) interleukin (IL)-4 and IL-5, which provide a positive feedback loop between the antigen-presenting cells (APCs) and the TH2 cells, and (2) IL-13, which is chemotactic and trophic to the eosinophils, and a major promoter of immunoglobulin (Ig)E synthesis and release by the B lymphocytes.…”

“…SM1 and STAT6 impact is additive, displays gender and familiar clustering, and leads to manyfold change in the incidence of reinfection (Isnard and Chevillard, 2008). Polymorphism of this gene has been associated with variance in the susceptibility to infection.…”

Co-infecção Plasmodium falciparum e Schistosoma haematobium: papel dos genes HLA não-clássicos de classe I (HLA-G, -E e -F) na suscetibilidade à malária

“…In endemic area, the natural evolution of the schistosomiasis infection depends on the age at the primary exposure and the intensity of the ongoing exposure (Gryseels et al 2006a;Isnard and Chevillard 2008b), which depends on the magnitude of disease transmission in a particular area (Dessein et al 1992;Kalinda et al 2017; Thomas and Short 2017). Several lines of evidence support the idea that the tropical and sub-tropical climates promote the species richness that can explain not only the high disease burden (Rosenzweig 1992;Schipper et al 2008;Dunn et al 2010;CDC 2017), but also intermediate host-parasite interaction (Daszak et al 2000).…”

“…Susceptibility to schistosomiasis may include the influence of environmental (Dessein et al 1992;Kalinda et al 2017; Thomas and Short 2017), genetic (Dessein et al 1992;Isnard and Chevillard 2008b;Mangano and Modiano 2014), and immune factors (details in section 1.4). Other factors such as age, gender, the use of tobacco (Dessein et al 1992;Remoue et al 2001;Isnard and Chevillard 2008b;Everts et al 2010;Zaghloul 2012;Mbanefo et al 2014) and even the pretreatment intensity (Mbanefo et al 2014) may also influence the susceptibility to S. haematobium infection.…”

“…Several studies have reported the influence of genetic factors on helminthiasis susceptibility (including schistosomiasis) (Isnard and Chevillard 2008b;Fumagalli et al 2010;Isnard et al 2011;Mangano and Modiano 2014). In 1991 and 1997, two independent groups reported that the major gene region associated with susceptibility to the schistosomiasis was located at 5q31-33 on chromosome 5 (Abel et al 1991;Marquet et al 1996).…”