Figure 1.

A schematic diagram describing the differential modulation of antigen-presenting cells in the early innate response and role of coinhibitory molecules in adaptive immunity in Leishmania pathogenesis is shown. (A) Virulent Leishmania donovani parasites are known to suppress antigen-presenting activity of DCs and macrophages. This is shown to be accompanied by reduction in the inflammatory cytokines as compared to infection with live-attenuated L. donovani parasites. These differences in the early interaction with the host APCs by the parasites determine the outcome, i.e., host susceptibility in case of virulent parasites or host resistance in case of attenuated parasites. (B) Previous studies have shown the role of coinhibitory molecules, such as CTLA-4, PD-L1, and CD200, in facilitating the parasite survival by inducing a restrained pro-inflammatory (T_H1) environment. The role of Tim-3 in Leishmania pathogenesis remains to be explored. The role of coinhibitory molecules in shaping the T cell immunity suggests that attenuated parasites might downregulate these pathways compared to virulent parasites in order to induce protective immunity. Blockade of the coinhibitory signals during priming by use of adjuvants might show potential improvement in the vaccine-induced immunity.