Anti-Leishmania activity of mucosal-associated invariant T-cells

Abstract Mucosal-associated invariant T (MAIT)-cells are restricted by MR1 and are known to contribute to protection from bacterial and viral infections. Here we show that MAIT-cells also play an important role in protection from visceral leishmaniasis-VL, caused by protozoan parasites of the Leishmania donovani complex. In response to L. infantum, human peripheral blood MAIT-cells produced TNF and IFN-γ and this was MR1-dependent. Since Leishmania spp. lack riboflavin biosynthesis, this suggests that novel MAIT-cell antigen(s) exist in the context of Leishmania-infection. In asymptomatic individuals, MAIT-cells also produced IL-17A, dependent on MR1, a cytokine signature associated with resistance to visceral Leishmaniasis. In mice, MAIT-cells reduced parasite burden during peak infection and decreased pathology. In summary, these results broaden our understanding of MAIT-cell immunity to include protection from parasitic infections with implications for MAIT-cell based therapeutics and vaccines. Leishmania is an ancient and clinically important pathogen such that it may have contributed to shaping MAIT-cell biology.