Tissue-specific IL-17-mediated immunity in experimental dermatophytosis

BURSTEIN V. L.; MENA C.; PRINZ, I.; CHIAPELLO L; GUASCONI L.; THEUMER M. G.; CERVI L.; BECCACECE I.; MASIH D.T.; GRUPPI A.

Congreso; 17th INFOCUS and I ISHAM Latin America Congress; 2019

Objective: To dissect the tissue-restricted antifungal immunity and the regulatory mechanisms of skin inflammation during an experimental model of epicutaneous infection with Microsporum dermatophytes.Methods: Eight to ten-week C57BL/6, IL-17RA-/-, IL-17A-GFP reporter, Lang-EGFPDTR male mice were infected on depilated and slightly abraded back with a Microsporum canis or M. gypseum (N. gypsea) hyphae suspension. On 8-day post-infection (dpi), mice were euthanized and the following parameters were evaluated: histopathological analysis, skin fungal burden (colony forming units/skin), extracutaneous fungal dissemination (organ culture), skin cell populations (flow cytometry), cytokine production by skin-draining lymph node (sdLN) cells and by epidermal cell populations (flow cytometry and ELISA). For conditional depletion of langerin-expressing cells (Lang+ cells), mice were intraperitoneally injected with diphtheria toxin (500 ng). For IFN-γ in vivo neutralization, mice were injected with anti-IFN-γ on 3 and 6 dpi (R4-6A2, 100 µg). To inhibit cell recruitment to skin, mice were injected with fingolimod (FTY720, 40 µg). T-student test or ANOVA were used for statistical analysis.Results: Experimental epicutaneous dermatophytosis mimics mild inflammatory human disease and is characterized by epidermal-limited invasion and neutrophil recruitment (p