Microbiota instruct IL-17A-producing innate lymphoid cells to promote skin inflammation in cutaneous leishmaniasis

• DOI: 10.1371/journal.ppat.1009693
• Publication Date: 2021-10-26T17:33:33Z
• Authors: Tej Pratap Singh; Augusto M. Carvalho; Laís Amorim Sacra...; Elizabeth A. Grice; Phillip Scott
• Keywords: 0303 health sciences; QH301-705.5; Interleukin-17; Leishmaniasis, Cutaneous; Dermatitis; Dendritic Cells; RC581-607; Immunity, Innate; 3. Good health; Mice; 03 medical and health sciences; Animals; Lymphocytes; Immunologic diseases. Allergy; Biology (General); Research Article; Skin

Innate lymphoid cells (ILCs) comprise a heterogeneous population of immune cells that maintain barrier function and can initiate a protective or pathological immune response upon infection. Here we show the involvement of IL-17A-producing ILCs in microbiota-driven immunopathology in cutaneous leishmaniasis. IL-17A-producing ILCs were RORγt+ and were enriched in Leishmania major infected skin, and topical colonization with Staphylococcus epidermidis before L. major infection exacerbated the skin inflammatory responses and IL-17A-producing RORγt+ ILC accumulation without impacting type 1 immune responses. IL-17A responses in ILCs were directed by Batf3 dependent CD103+ dendritic cells and IL-23. Moreover, experiments using Rag1-/- mice established that IL-17A+ ILCs were sufficient in driving the inflammatory responses as depletion of ILCs or neutralization of IL-17A diminished the microbiota mediated immunopathology. Taken together, this study indicates that the skin microbiota promotes RORγt+ IL-17A-producing ILCs, which augment the skin inflammation in cutaneous leishmaniasis.