Commensal microbiota induces IL-17A-producing innate lymphoid cells that augment skin inflammation in cutaneous leishmaniasis

Abstract

Abstract Innate lymphoid cells (ILCs) comprise a heterogeneous population of immune cells that are enriched at barrier surfaces where they quickly respond to host, microbial or environmental stimuli to promote immunity. Whether ILCs are activated during a cutaneous leishmaniasis infection, and whether the skin microbiota might influence ILC responses, is unknown. To address this issue, we studied ILC development in Leishmania major infected mice as well in bacteria colonized mice subsequently infected with L. major. IL-17A-producing but not IFN-g and IL-13-producing ILCs were enriched in early L. major infected skin. Topical colonization with Staphylococcus epidermidis or Staphylococcus xylosus before L. major infection increased the number of IL-17A+ ILCs in the skin and enhanced the inflammatory response. Microbiota colonization did not influence the IFN-g production from CD4+ T cells or the parasite load. In addition, IL-17A-production from ILCs was regulated by Batf3 dependent CD103+ dendritic cells, and experiments using Rag1−/− mice demonstrated that ILC17s were sufficient in driving the microbiota dependent inflammatory responses in L. major infected skin. Depletion of ILCs or neutralization of IL-17A in Rag1−/− mice diminished the microbiota mediated inflammatory responses of L. major infected skin. Taken together, this study indicates that the skin microbiota promotes IL-17A-producing ILCs, which drives increased inflammatory responses in cutaneous leishmaniasis.