Abstract
The parasitic worms, Schistosoma mansoni and Schistosoma japonicum, reside in the mesenteric veins, where they release eggs that induce a dramatic granulomatous response in the liver and intestines. Subsequently, infection may further develop into significant fibrosis and portal hypertension. Over the past several years, uncovering the mechanism of immunopathology in schistosomiasis has become a major research objective. It is known that T lymphocytes, especially CD4+ T cells, are essential for immune responses against Schistosoma species. However, obtaining a clear understanding of how T lymphocytes regulate the pathological process is proving to be a daunting challenge. To date, CD4+ T cell subsets have been classified into several distinct T helper (Th) phenotypes including Th1, Th2, Th17, T follicular helper cells (Tfh), Th9, and regulatory T cells (Tregs). In the case of schistosomiasis, the granulomatous inflammation and the chronic liver pathology are critically regulated by the Th1/Th2 responses. Animal studies suggest that there is a moderate Th1 response to parasite antigens during the acute stage, but then, egg-derived antigens induce a sustained and dominant Th2 response that mediates granuloma formation and liver fibrosis. In addition, the newly discovered Th17 cells also play a critical role in the hepatic immunopathology of schistosomiasis. Within the liver, Tregs are recruited to hepatic granulomas and exert an immunosuppressive role to limit the granulomatous inflammation and fibrosis. Moreover, recent studies have shown that Tfh and Th9 cells might also promote liver granulomas and fibrogenesis in the murine schistosomiasis. Thus, during infection, T-cell subsets undergo complicated cross-talk with antigen presenting cells that then defines their various roles in the local microenvironment for regulating the pathological progression of schistosomiasis. This current review summarizes a vast body of literature to elucidate the contribution of T lymphocytes and their associated cytokines in the immunopathology of schistosomiasis.
Highlights
Human schistosomiasis is a zoonotic parasitic disease caused by schistosomes, which are digenetic trematodes
The difference between acute and chronic schistosomiasis is that there is no correlation between percentages of programmed death 1 (PD-1)+CXCR5+CD4+ T follicular helper cells (Tfh) cells, memory B cells, or the level of immunoglobulin G (IgG) specific to S. japonicum antigen in acute schistosomiasis patients; frequency of PD-1+CXCR5+CD4+ Tfh cells is positively correlated to the levels of IL-21 in sera and the levels of soluble egg antigens (SEAs)-specific antibody in chronic schistosomiasis patients [93, 94]
Recent studies showed that Th17 and Tfh are involved in the immune response of acute cases [71, 94]
Summary
Human schistosomiasis is a zoonotic parasitic disease caused by schistosomes, which are digenetic trematodes. IL-12/IL-10 double-deficient mice with highly polarized Th2-type cytokine responses develop increased hepatic fibrosis and mortality during the chronic stages of infection [18] Both Th1 and Th2 phases are downregulated by endogenous IL-10, which is produced by macrophages and T cells [55]. Numerous studies have promoted our understanding of the basic immunopathogenesis of schistosomiasis; it should be noted that schistosome-induced liver immunopathologies are associated with Schistosoma species and host Examples of this include that the cellular composition of the S. japonicum egg-induced granulomas are mainly neutrophils, whereas S. mansoni-induced granulomas consist of a higher ratio of mononuclear cells and eosinophils, with lower numbers of neutrophils [76, 77]. Mouse strain-dependent schistosomiasis pathology may arise from the difference of Ag-specific Th responses [62], such as S. mansoniinfected CBA mice displaying exacerbated granulomatous lesions when compared to C57BL/6 mice because of high ratios of IL-17-producing cells in the granulomas [62]
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