Myeloid‐derived suppressor cells help protective immunity to Leishmania majorinfection despite suppressed T cell responses

Infection with Leishmania majorelicits myeloid‐derived suppressor cells, which kill Leishmania parasites despite suppressed T‐cell proliferation. Th1/Th2 cytokines play a key role in immune responses to Leishmania majorby controlling macrophage activation for NO production and parasite killing. MDSCs, including myeloid precursors and immature monocytes, produce NO and suppress T cell responses in tumor immunity. We hypothesized that NO‐producing MDSCs could help immunity to L. majorinfection. Gr1hi(Ly6Chi) CD11bhiMDSCs elicited by L. majorinfection suppressed polyclonal and antigen‐specific T cell proliferation. Moreover, L. major‐induced MDSCs killed intracellular parasites in a NO‐dependent manner and reduced parasite burden in vivo. By contrast, treatment with ATRA, which induces MDSCs to differentiate into macrophages, increased development of lesions, parasite load, and T cell proliferation in draining LNs. Altogether, these results indicate that NO‐producing MDSCs help protective immunity to L. majorinfection, despite suppressed T cell proliferation.