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

BURSTEIN VL; GUASCONI L; BECCACECE I; THEUMER MG; HERRERO M; MENA C; MASIH DT; CHIAPELLO L S

LXIV Reunión Anual de la Sociedad Argentina de Inmunología (SAIC-SAI-SAFE).

Congreso; LXIV Reunión Anual de la Sociedad Argentina de Inmunología (SAIC-SAI-SAFE).; 2016

Sociedad Argentina de Inmunología.

Microsporum canis is a zoophilic dermatophyte fungus, highly prevalent in immunocompetent children causing superficial infections of the scalp and body. Dermatophytes have been also reported to invade beyond the epidermis, causing deep mycosis. The in vivo role of IL-17 signaling and Langerhans cells are currenly unknown during dermatophytic infections.Objective: To determine the impact of IL-17 signaling in the outcome of experimentaldermatophytosis in mice and the role of Langerhans cells (LC) to establish the skin antifungal immunity.Wild type (WT), IL-17RA -/- (KO), IL-17A/F -/- (KO) and LangDTREGFP C57BL/6 mice were epicutaneously infected with M. canis. For selective depletion of LC, 5 days before infection LangDTREGFP were intraperitoneally injected with difteric toxin (DT). 4, 8, 18 and 45 days post-infection (d.p.i) histopathological analysis, skin fungal burden (HPLC ergosterol quantification) and extracutaneous fungal dissemination were determined. CD11b + Ly6G+ and T CD4 + , T CD8 + , Tγ and B cell populations and its cytokine production were analyzed (ELISA or intracellular staining and FACS) in skin cell suspensions or in skin draining lymph nodes cells(sdLN). Cytokine production were also measured in epidermal sheets explants cultures with or without M. canis hyphae.Wild type mice resolved infection by 20 dpi, showing features of human dermatophytosis, mainly characterized by a significant neutrophil (PMN) infiltrate into the skin. WT mice specific generate TCD4+ IL-17- producing sdLN, beginning at 8 dpi. M. canis hyphae stimulate 17 A/F, IL-23, IL-6, IL-12 e IL-10 production by epidermal cells and purified LC promoted only IL-17 A/F production by allogenic lymphocytes. IL-17- deficient mice resolved infection similar to WT, but they showed higher skin fungal burden, more intense inflammatory response and PMN infiltrate in the epidermis, and a shift to INF production by sdLN, compared to WT mice. In vivoblocking of INF- partially inhibited the exaggerated cutaneous inflammation in infected IL- 17RAKO mice. LC depletion in M. canis infected LangDTREGFP mice demonstrate the central role of LC to induce the Th17 adaptative immune response.IL-17 signaling protect against the superficial infection and the exacerbated Th1 inflammation, but it is not involved in PMN recruitment into the skin and the control of extracutaneous fungal dissemination.