Interleukin 17-producing epidermal cell subsets in experimental Microsporum canis dermatophytosis

GUASCONI LORENA; THEUMER MARTIN; BURSTEIN VERONICA; GRUPPI ADRIANA; CHIAPELLO LAURA; BECCACECE IGNACIO; MENA CRISTIAN; CERVI LAURA

Buenos Aires

Congreso; Reunión Conjunta de Sociedades de Biociencias; 2017

Microsporum canis is a dermatophyte fungus that causes highly prevalent skin infections in immunocompetent children. We previously demonstrated that a Th17 response is induced after epicutaneous infection of C57BL/6 mice with M. canis and that IL-17-mediated immunity prevents fungal proliferation in skin. However, the mechanisms of dermatophyte recognition and skin cell populations involved in IL-17-driven host defense remain unknown.The aim of this study was to determine skin cell sources of IL-17A and the role of TLR-2 and Dectin-1 receptors in the protective immunity against M. canis infection.Wild type (WT), IL-17GFP reporter, IL-17RAKO, TLR-2KO and Dectin-1KO C57BL/6 mice were epicutaneously infected with M. canis hyphae or treated with saline. After 8 days of infection, skin fungal burden was determined and IL-17A-producing epidermal cell populations were evaluated by FACS with anti-CD45, CD11b, Ly6G, TCR, TCRγ, CD3, CD4 or CD8 antibodies. Cytokine production by epidermal sheets explants was quantified in supernatants (ELISA) after 48h of culture with or without M. canis.We observed that, in M canis-infected IL-17GFP reporter mice, CD45+TCR+ and TCRγ+ epidermal cells were the main IL-17A producing-cells. No IL-17 expression was observed in keratinocytes, neutrophils or macrophages. In addition, after culture with epidermal sheets explants, M. canis significantly increased IL-6 and IL-1 (IL-17-type response cytokines) respect to controls in medium alone. Furthermore, infected IL-17RA KO mice showed a significant increase in fungal burden respect to WT mice (38200 ± 13980 vs 867 ± 392 CFU/g, p < 0.05). TLR-2 or dectin-1 deficient mice showed a similar fungal burden and IL-17-producing T cell frequency compared to infected WT mice. This study is the first characterization of skin IL-17-producing cells in dermatophytosis and it strongly suggests that TLR-2 or Dectin-1 receptors are not involved in the IL-17-driven host protection against M. canis.