Leishmaniasis is a chronic progressive disease usually controlled by TH1-type IFN-γ producing cells. Human or murine leishmaniasis can progress despite the presence of T cells capable of producing IFN-γ. It is reported that CD8 cells in humans with visceral leishmaniasis (VL) express markers of T cell exhaustion. We hypothesized that myeloid cells play a role in exhausting T cells at the local sites of Leishmania species infection inhibiting proper adaptive responses. We addressed this hypothesis in BALB/c models of cutaneous leishmaniasis (CL) or VL caused by L. major or L. donovani infection, respectively. We examined inhibitory receptors PD1, LAG3, CTLA4 and TIM3 on lymphoid cells, and counter-receptors PDL1, MHCII, and CD80 in myeloid cell by flow cytometry throughout 4 weeks of infection. Both models showed significant increases in PD-1 in circulating dendritic cells after 1 week of infection. However, after 3–4 weeks when infection was chronic, PDL-1 was expressed on neutrophils in the blood and at the local sites of infection (infected ear tissue and draining lymph nodes of L. major infected mice; spleen cells of L. donovani-infected mice). Furthermore, PD1 was expressed on both CD4 and CD8 T cells in blood and lymph nodes of mice infected with L. major at the same time. In contrast, only CD4 T cells, but not CD8 T cells) displayed higher PD-1 in blood and spleens of mice infected with L. donovani. In conclusion, both disease models elicited the exhaustion counter-receptor PDL1 on neutrophils in the blood and the local site of parasite growth. The T cell exhaustion marker PD1 was expressed on T cells at the same sites, although both CD4 and CD8 T cells displayed PD1 in the CL model, whereas PD1 expression was more profound on CD4 T cells in the VL model.

Leishmaniasis is a spectrum of diseases caused by Leishmania species protozoa that is most common in warm climates, coinciding with impoverished regions. Visceral leishmaniasis is a potentially fatal disease in which parasites infect reticuloendothelial organs and cause progressive wasting and immunocompromise.

No abstract