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

Area of Science:

• Immunology
• Dermatology
• Microbiology

Background:

• Fungal skin infections (dermatophytosis) pose a significant global health challenge.
• Understanding cutaneous immunity against dermatophytes is crucial but limited.
• Previous work identified IL-17RA signaling's role in combating Microsporum canis infections.

Purpose of the Study:

• To investigate the cellular sources of IL-17A during Nannizzia gypsea dermatophytosis.
• To elucidate the role of T cells and innate lymphoid cells in cutaneous antifungal immunity.
• To determine the contribution of lymph node priming to local skin defenses.

Main Methods:

• Utilized a mouse model of epicutaneous Nannizzia gypsea infection.
• Employed flow cytometry to identify IL-17A producing T cell subsets (γδTCRint, CD8/CD4 double-negative βTCR+).
• Administered fingolimod to restrict lymphocyte trafficking and used Rag1-/- and Rag2-/-Il2rg-/- mice to assess immune cell contributions.

Main Results:

• Skin γδT and CD8/CD4 double-negative βTCR+ T cells were identified as primary IL-17A producers.
• These IL-17A+ T cells displayed activated/memory phenotypes, including proliferating tissue-resident cells.
• Local antifungal defenses were effective even when lymphocyte trafficking was restricted, independent of lymph node priming.
• Rag1-/- mice controlled infection with enhanced IL-17A from innate lymphoid cells (ILCs).
• Rag2-/-Il2rg-/- mice, lacking T, B, and ILCs, showed high susceptibility, confirming ILC sufficiency in T-cell-deficient settings.

Conclusions:

• Skin γδT cells and specific αβT cell subsets are key producers of IL-17A during Nannizzia gypsea infection.
• Innate lymphoid cells play a crucial role in antifungal immunity, particularly in the absence of T cells.
• Cutaneous immunity against dermatophytosis involves a coordinated response between adaptive and innate immune cells within the skin.