Abstract
Leishmania amazonensis is an etiological agent of diffuse cutaneous leishmaniasis in South America. In murine models, dysfunctional expansion of effector T cells and Th1 response exhaustion are linked to pathogenesis, while regulatory T cells (Tregs) promote lesion resolution. This study examined the roles of PD-1 and PD-L1 in the immunopathogenesis of L. amazonensis infection in C57BL/6 mice. We found a significant increase in PD-1 and PD-L1 expression in infected tissues, correlating with increased PD-L1+CD11c+ dendritic cells (DCs) and PD-1+CD4+ T cells in draining lymph nodes. Infection of bone marrow-derived DCs (BMDCs) with promastigotes and amastigotes revealed that PD-L1 expression was induced by mTOR, partially by STAT3, PI3K, and MAPK. Infected BMDCs in vitro inhibited Th1 cell expansion compared to non-infected BMDCs. In vivo experiments showed that PD-L1-/- mice exhibited increased Th1 responses, reduced lesion sizes, and lower parasite loads. These results suggest a non-protective role for PD-1/PD-L1 signaling in regulating local immune responses during L. amazonensis infection, providing new insights into immune regulation in New World cutaneous leishmaniasis.