Cutaneous Innate Lymphoid Populations Drive IL-17A-Mediated Immunity in Nannizzia gypsea Dermatophytosis.

Abstract

Fungal skin infections significantly contribute to the global human disease burden, yet our understanding of cutaneous immunity against dermatophytes remains limited. Previously, we developed a model of epicutaneous infection with Microsporum canis in C57BL/6 mice, which highlighted the critical role of IL-17RA signaling in antidermatophyte defenses. In this study, we expanded our investigation to the human pathogen Nannizzia gypsea and demonstrated that skin γδTCRand CD8/CD4 double-negative βTCRT cells are the principal producers of IL-17A during dermatophytosis. These IL-17AT cells exhibited an activated/memory phenotype, including a subset of proliferating tissue-resident cells. Notably, restriction of lymphocyte trafficking after fingolimod administration in infected mice did not lead to increased susceptibility, indicating that local antifungal defenses are independent of T-cell priming in lymph nodes. In addition, Rag1mice lacking T and B lymphocytes effectively controlled infection and exhibited increased IL-17A production by innate lymphoid cells. Furthermore, Rag2Il2rgmice, devoid of T, B, and innate lymphoid cells, were highly susceptible to dermatophytosis compared with Rag2or wild-type mice, demonstrating that innate lymphoid cells are sufficient to antifungal defenses in T-cell-deficient mice. In conclusion, our study underscores the coordinated interplay between skin γδT, αβT, and innate lymphoid cell subsets in controlling primary N gypsea dermatophytosis.