Role of Th17 and CD4+CD25+FOXP3+ regulatory T cells responses during experimental infection with Leishmania infantum chagasi

Abstract

Leishmania infantum chagasi (Lic) is the etiologic agent of visceral leishmaniasis (VL) in Brazil. While Regulatory T cells (Treg) have been associated with suppression of effector cells, favoring the survival of parasite, Th17 is related with the protection against L. donovani infection in humans. However, both cellular participations in rodent models are unknown. Thus, our aim is to investigate the role of Th17 and Treg in Lic experimental infection as well as the mechanisms involved in such subtypes differentiation. To intend this propose, initially we will perform the expression kinetic of FOXP3 and ROR-³t, Treg and Th17 markers, respectively, in C57BL/6 infected mice. Cytokine production focusing on both subtype drive, such as IL-1², TGF-², IL-6, IL-23 will be measured on spleen cells culture supernatant. Afterwards, analysis of parasite load, inflammatory infiltrated and cytokines production will be evaluated in the spleen and liver from infected IL-17-/-, IL-22-/-, IL-6-/- and IL-23-/- mice. Furthermore, bone-marrow derived macrophages from IL-17-/-, IL-22-/-, IL-6-/- and IL-23-/- will be infected with parasite to determine leishmanicidal activity (NO production and amastigotes numbers). Finally, the Treg depletion with antibody against GITR will be performed into WT and IL-17-/- infected mice to evaluate the parasite number, cytokine production and inflammatory infiltration. The determination of the mechanistics by which parasite interacts with the host defense may open new perspectives for the treatment and prophylaxis for VL.