IN VIVO ROLE OF LANGERHANS CELLS AND IL-17 IMMUNITY IN EXPERIMENTAL Microsporum canis SKIN INFECTION

BECACECCE I.; MENA C.; GUASCONI L.; HERRERO M.; CHIAPELLO L.; BURSTEIN V.L.; THEUMER M.G.; MASIH D.

Mar del Plata

Congreso; SAIC SAI SAFE 2016; 2016

Sociedad Argentina de Investigación Clínica, Sociedad Argentina de Inmunología, Sociedad Argentina de Farmacología Experimental

Microsporum canis is a dermatophyte fungus highly prevalent in immunocompetentchildren that causes superficial infections. However, invasion beyond epidermishas also been reported. The in vivo role of IL-17 and Langerhanscells (LC) during dermatophytosis is currently unknown.Objective:To determine the impact of IL-17 signaling in experimental dermatophytosis inmice 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, diphtheriatoxin was injected 3 days before infection. On 4, 8 and 18 days post-infection(dpi) histopathological analysis, skin fungal burden (HPLC ergosterolquantification) and fungal dissemination were determined. CD11b+Ly6G+,T cells populations and cytokine production were analyzed (ELISA, FACS) in epidermisor skin-draining lymph node (sdLN) cells. Cytokines were also measured in epidermalsheet explants incubated with M. canis.WT mice resolved infection by 20 dpi showing featuresof human dermatophytosis. The response was mainly characterized by significantneutrophilic 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 productionby epidermal cells and purified LC promoted only IL-17A/F production by allogeneiclymphocytes. IL-17 deficient mice resolved infection similar to WT, but showedhigher skin inflammation and fungal burden and a shift to IFN-γ production insdLNs, compared to WT mice. In vivo IFN-γ blocking partially inhibited the exacerbated cutaneousinflammation and LC depletion in Lang-EGFPDTR mice showed significant decreasein M. canis specific IL-17-producingCD4+ T cells.Langerhans cells induce Th17 antifungal immunity. IL-17signaling protects against M. canis infectionand the exacerbated Th1 inflammation, but is not involved in PMN recruitment toskin or in control of extracutaneous fungal dissemination.