Immunity and immunosuppression in experimental visceral leishmaniasis.

H Goto,J.A.L Lindoso

doi:10.1590/s0100-879x2004000400020

Abstract

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.

Highlights

Protozoa of the genus Leishmania cause cutaneous, mucocutaneous or visceral diseases in man depending on the species of the parasite and the host immune response
It was shown that in vitro infection of macrophages by Leishmania renders them resistant to apoptosis [60]. We studied this phenomenon in vivo in hamsters with visceral leishmaniasis and observed that apoptosis is induced in macrophages by L. (L.) chagasi infection in the initial phase
The immunological responses induced during experimental visceral leishmaniasis are markedly different from those induced in cutaneous leishmaniasis

Summary

Introduction

Protozoa of the genus Leishmania cause cutaneous, mucocutaneous or visceral diseases in man depending on the species of the parasite and the host immune response. 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.

Results

Conclusion