Immunity and immunosuppression in experimental visceral leishmaniasis.
Leishmaniasis is a disease caused by protozoa of the genus Leishmania, and visceral leishmaniasis is a form in which the inner organs are affected. Since knowledge about immunity in experimental visceral leishmaniasis is poor, we present here a review on immunity and immunosuppression in experimental visceral leishmaniasis in mouse and hamster models. We show the complexity of the mechanisms involved and differences when compared with the cutaneous form of leishmaniasis. Resistance in visceral leishmaniasis involves both CD4+ and CD8+ T cells, and interleukin (IL)-2, interferon (IFN)-gamma, and IL-12, the latter in a mechanism independent of IFN-gamma and linked to transforming growth factor (TGF)-beta production. Susceptibility involves IL-10 but not IL-4, and B cells. In immune animals, upon re-infection, the elements involved in resistance are different, i.e., CD8+ T cells and IL-2. Since one of the immunopathological consequences of active visceral leishmaniasis in humans is suppression of T-cell responses, many studies have been conducted using experimental models. Immunosuppression is mainly Leishmania antigen specific, and T cells, Th2 cells and adherent antigen-presenting cells have been shown to be involved. Interactions of the co-stimulatory molecule family B7-CTLA-4 leading to increased level of TGF-beta as well as apoptosis of CD4+ T cells and inhibition of macrophage apoptosis by Leishmania infection are other components participating in immunosuppression. A better understanding of this complex immune response and the mechanisms of immunosuppression in experimental visceral leishmaniasis will contribute to the study of human disease and to vaccine development.
Goto
H
H
Laboratório de Soroepidemiologia e Imunobiologia, Instituto de Medicina Tropical de São Paulo e Departamento de Medicina Preventiva, Faculdade de Medicina, Universidade de São Paulo, Sao Paulo, SP, Brazil. hgoto@usp.br
Lindoso
J A L
JA
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D006224:Cricetinae; D016207:Cytokines / Q000276:immunology*; D004195:Disease Models, Animal; D007165:Immunosuppression Therapy; D007898:Leishmaniasis, Visceral / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D013601:T-Lymphocytes / Q000276:immunology*; D015291:Transforming Growth Factors / Q000276:immunology*
D016207:Cytokines; D015291:Transforming Growth Factors