In vivo role of Langerhans cells and IL-17 immunity in experimental M. canis skin infection.

BURSTEIN, VL; THEUMER, MG; MASIH, DT; GUASCONI, L; HERRERO, M; CHIAPELLO, LS; BECCACECE, I; MENA, CJ

Mar del Plata

Congreso; SAIC, SAI, SAFE 2016; 2016

SAIC, SAI, SAFE

Microsporum canis is a dermatophyte fungus highly prevalent in immunocompetent children that causes superficial infections. However, invasion beyond epidermis has also been reported. The in vivo role of IL-17 and Langerhans cells (LC) during dermatophytosis is currently unknown.Objective: To determine the impact of IL-17 signaling in experimental dermatophytosis in mice and the role of LC in establishing skin antifungal immunity. Wild type (WT), IL-17RAKO, IL17A/FKO or Lang-EGFPDTR C57BL/6 mice were epicutaneously infected with M. canis. For LC depletion, diphtheria toxin was injected 3 days before infection. On 4, 8 and 18 days post-infection (dpi) histopathological analysis, skin fungal burden (HPLC ergosterol quantification) and fungal dissemination were determined. CD11b+Ly6G+, T cells populations and cytokine production were analyzed (ELISA, FACS) in epidermis or skin-draining lymph node (sdLN) cells. Cytokines were also measured in epidermal sheet explants incubated with M. canis.WT mice resolved infection by 20 dpi showing features of human dermatophytosis. The response was mainly characterized by significant neutrophilic skin infiltrate and IL-17-producing CD4+ T cells in sdLNs by 8 dpi. M. canis hyphae stimulated IL-17A/F, IL-23, IL-6, IL-12 and IL-10 production by epidermal cells and purified LC promoted only IL-17A/F production by allogeneic lymphocytes. IL-17 deficient mice resolved infection similar to WT, but showed higher skin inflammation and fungal burden and a shift to IFN-γ production in sdLNs, compared to WT mice. In vivo IFN-γ blocking partially inhibited the exacerbated cutaneous inflammation and LC depletion in Lang-EGFPDTR mice showed significant decrease in M. canis specific IL-17-producing CD4+ T cells.Langerhans cells induce Th17 antifungal immunity. IL-17 signaling protects against M. canis infection and the exacerbated Th1 inflammation, but is not involved in PMN recruitment to skin or in control of extracutaneous fungal dissemination.