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

BURSTEIN VL; BECCACECE I; CHIAPELLO LS

Salvador

Congreso; International Congress of International Society of Human and Animal Mycology (ISHAM) and Infecciones Fúngicas en la Práctica Clínica de Latino América (INFOCUS); 2019

ISHAM

ObjectiveTo investigate the tissue-restricted antifungal immunity and the regulatory mechanisms of skin inflammation during an experimental model of epicutaneous infection with Microsporum dermatophytes.MethodsEight 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. After diferent days 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 lymphocyte recruitment to skin, mice were injected with fingolimod (FTY720, 40 µg). T-student test or ANOVA were used for statistical analysis.ResultsExperimental epicutaneous dermatophytosis mimics mild inflammatory human disease and is characterized by epidermal-limited invasion and neutrophil recruitment (p