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

CERVI L.; MENA C.; BECCACECE I.; THEUMER M. G.; GUASCONI L.; CHIAPELLO L; GRUPPI A.; BURSTEIN V. L.

Ciudad Autónoma de Buenos Aires

Congreso; Reunión Conjunta de Sociedades de Biociencias SAIC-SAIB-SAI-SAA-SAB-SAB-SAFE-SAFIS-SAH-SAP; 2017

SAIC, SAIB, SAI, SAA, SAB, SAB, SAFE, SAFIS, SAH, SAP.

Microsporum canis is a dermatophyte fungus that causes highlyprevalent skin infections in immunocompetent children. We previouslydemonstrated that a Th17 response is induced after epicutaneousinfection of C57BL/6 mice with M. canis and that IL-17-mediatedimmunity prevents fungal proliferation in skin. However, themechanisms of dermatophyte recognition and skin cell populationsinvolved in IL-17-driven host defense remain unknown.The aim of this study was to determine skin cell sources of IL-17Aand the role of TLR-2 and Dectin-1 receptors in the protective immunityagainst M. canis infection.Wild type (WT), IL-17GFP reporter, IL-17RAKO, TLR-2KO andDectin-1KO C57BL/6 mice were epicutaneously infected with M.canis hyphae or treated with saline. After 8 days of infection, skinfungal burden was determined and IL-17A-producing epidermal cellpopulations were evaluated by FACS with anti-CD45, CD11b, Ly6G,TCRb, TCRγd, CD3, CD4 or CD8 antibodies. Cytokine productionby 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+TCRb+ and TCRγd+ epidermal cells were the main IL-17Aproducing-cells. No IL-17 expression was observed in keratinocytes,neutrophils or macrophages. In addition, after culture with epidermalsheets explants, M. canis significantly increased IL-6 and IL-1b (IL-17-type response cytokines) respect to controls in medium alone.Furthermore, infected IL-17RA KO mice showed a significant increasein fungal burden respect to WT mice (38200 ± 13980 vs 867 ±392 CFU/g, p < 0.05). TLR-2 or dectin-1 deficient mice showed asimilar fungal burden and IL-17-producing T cell frequency comparedto infected WT mice.This study is the first characterization of skin IL-17-producing cellsin dermatophytosis and it strongly suggests that TLR-2 or Dectin-1receptors are not involved in the IL-17-driven host protection against M. canis.