In vivo role of INF--mediated skin immune response in experimental dermatophytosis in IL-17RA deficient mice

BURSTEIN VL; BECCACECE I; GUASCONI L; MENA C; ORELLANO AGOSTINA; GRUPPI A; THEUMER, MG; CERVI L; CHIAPELLO LS

Congreso; Reunión Conjunta SAIC SAI SAFIS 2018; 2018

Microsporum canis is a dermatophyte fungus that causes superficialinfections and is highly prevalent among immunocompetentchildren. Previously, we demonstrated that M. canis induces a type17 immunity in vivo that controls fungal proliferation in skin anddown-modulates an antigen-specific IFN-γ response.Objective: To evaluate the role of IFN-γ in the experimental dermatophytosisoutcome in absence of IL-17RA signaling.Wild type (WT) and IL-17RA-deficient C57BL/6 (KO) mice wereepicutaneously infected with M. canis hyphae. On different dayspost-infection (dpi), histopathology, CD11b+Ly6G+ population (neutrophils,FACS), cytokine analysis (ELISA, FACS) and fungal burden(colony forming units/ g skin) were determined in epidermis.For IFN-γ blocking, anti IFN-γ antibody (BioXCell, 400 μg/mice) orisotype control (IC) was injected (intraperitoneally) on 3 and 6 dpi.We observed that by 6 and 8 dpi, infected KO showed an increase infungal burden (p<0.01), neutrophil recruitment (p<0.0001), CXCL1expression (p<0.05) and TNF (p<0.002) in the skin, compared toWT. After IFN-γ blocking in KO and by 8 dpi, unexpectedly, therewas a reduction in fungal burden (p<0.005 vs WT; p<0.05 vs ICtreated-KO) with a decrease in neutrophil infiltration (p<0.0001) andTNF production (p<0.001 vs WT, p<0.0001 vs IC-KO). In contrast,these mice showed an increased production of IL-17 pathway-relatedcytokines such as IL-23 (p<0.001 vs WT and IC-KO) and IL-22 (p<0.005 vs WT, p<0.05 vs IC-KO), among others, by epidermalcells.Our results suggest that, in the absence of IL-17 signaling, there isa deregulated Th1 response that promotes M. canis skin infection.