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

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 γδTCR^int and CD8/CD4 double-negative βTCR⁺ T cells are the principal producers of IL-17A during dermatophytosis. These IL-17A⁺ T 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, Rag1^-/- mice lacking T and B lymphocytes effectively controlled infection and exhibited increased IL-17A production by innate lymphoid cells. Furthermore, Rag2^-/-Il2rg^-/- mice, devoid of T, B, and innate lymphoid cells, were highly susceptible to dermatophytosis compared with Rag2^-/-or 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.