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 anti-dermatophyte defenses. Here, we expanded our investigation to the human pathogen Nannizzia gypsea and demonstrated that skin γδTCRint 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 following 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. Additionally, Rag1-/- mice lacking T and B lymphocytes effectively controlled infection and exhibited increased IL-17A production by innate lymphoid cells (ILCs). Furthermore, Rag2-/-Il2rg-/- mice, devoid of T, B, and ILCs cells, were highly susceptible to dermatophytosis compared to Rag2-/- or WT mice, demonstrating that ILCs are sufficient to antifungal defenses in T cell-deficient mice. In conclusion, our study underscores the coordinated interplay between skin γδT, αβT, and ILCs subsets in controlling primary N. gypsea dermatophytosis.
Keywords: DERMATOPHYTOSES; ILC3; MYCOSES; T CELLS.
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