Immunoactivation and immunopathogeny during active visceral leishmaniasis.
Visceral leishmaniasis is caused by protozoan parasites of the Leishmania donovani complex. During active disease in humans, high levels of IFN-gamma and TNF-alpha detected in blood serum, and high expression of IFN-gamma mRNA in samples of the lymphoid organs suggest that the immune system is highly activated. However, studies using peripheral blood mononuclear cells have found immunosuppression specific to Leishmania antigens; this poor immune response probably results from Leishmania antigen-engaged lymphocytes being trapped in the lymphoid organs. To allow the parasites to multiply, deactivating cytokines IL-10 and TGF-beta may be acting on macrophages as well as anti-Leishmania antibodies that opsonize amastigotes and induce IL-10 production in macrophages. These high activation and deactivation processes are likely to occur mainly in the spleen and liver and can be confirmed through the examination of organ samples. However, an analysis of sequential data from studies of visceral leishmaniasis in hamsters suggests that factors outside of the immune system are responsible for the early inactivation of inducible nitric oxide synthase, which occurs before the expression of deactivating cytokines. In active visceral leishmaniasis, the immune system actively participates in non-lymphoid organ lesioning. While current views only consider immunocomplex deposition, macrophages, T cells, cytokines, and immunoglobulins by diverse mechanism also play important roles in the pathogenesis.
Goto
Hiro
H
Laboratory of Seroepidemiology and Immunobiology, Instituto de Medicina Tropical de São Paulo, Universidade de São Paulo, SP, Brazil. hgoto@usp.br
Prianti
Maria das Graças
Md
D000818:Animals; D006224:Cricetinae; D016207:Cytokines / Q000096:biosynthesis*; D004285:Dogs; D006801:Humans; D007111:Immunity, Cellular; D007132:Immunoglobulin Isotypes / Q000276:immunology; D007893:Leishmania donovani / Q000276:immunology*; D007898:Leishmaniasis, Visceral / Q000276:immunology*; D008262:Macrophage Activation / Q000276:immunology; D009569:Nitric Oxide / Q000096:biosynthesis / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D016207:Cytokines; D007132:Immunoglobulin Isotypes; D009569:Nitric Oxide