Kurzfassung

Protective immunity in cutaneous leishmaniasis is dependent on the development of IFNg+ CD4+ Th1 and IFNg secreting CD8+ Tc1 cells. On the other hand, thymus-derived regulatory T cells (tTreg) promote parasite persistence, which leads to worsening of disease and contributes to the maintenance of memory responses. IL-17A, released primarily from CD4+ T (Th17) cells and gd T cells, contributes to disease susceptibility. The balance between induction of pathogenic vs. protective T cells is...Protective immunity in cutaneous leishmaniasis is dependent on the development of IFNg+ CD4+ Th1 and IFNg secreting CD8+ Tc1 cells. On the other hand, thymus-derived regulatory T cells (tTreg) promote parasite persistence, which leads to worsening of disease and contributes to the maintenance of memory responses. IL-17A, released primarily from CD4+ T (Th17) cells and gd T cells, contributes to disease susceptibility. The balance between induction of pathogenic vs. protective T cells is orchestrated by L. major-infected dendritic cells (DC). These infected DCs dictate the nature of the T cells response and hence disease outcome by secreting proinflammatory cytokines. In order to better understand how to modulate T cell differentiation in vivo using the model pathogen L. major, we will investigate the role of different DC- and T cell-derived cytokines for the differentiation of Th17 and Treg cells. To better understand the dynamic of protective or pathogenic T cells during infection, we will use mice that allow us to follow the development as well as the fate of IL-17A-, IL-17F- and IFNg-producing T cells. The effect of deletion of all IL-17 producing cells as well as IL-10+ Treg will be assessed. To study the development of antigen-specific Th17 and Treg, we will use mice where T cells lack expression of the receptors that respond to IL-1 or IL-6, and evaluate the role of IL-1 and IL-6 during infection with L. major. Finally, in order to better understand the role of pro-inflammatory cytokines in infection-associated pathogenicity, we will use mice where keratinocytes lack specifically the receptors of IL-1, IL-6 or IL-17, and study L. major infection disease outcome and which genes are regulated by these cytokines in keratinocytes during infection. Together, these in vivo systems should allow us a better understanding of the cytokines that regulate the T cell response during L. major infection.» weiterlesen» einklappen