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

BURSTEIN VL; BECCACECE I; GUASCONI L; MENA C; ORELLANO A; GRUPPI A; THEUMER MG; CHIAPELLO LAURA S.

Mar del Plata

Congreso; LXVI Reunión Anual de la Sociedad Argentina de Inmunología. SAI-SAIC-SAFIS; 2018

Sociedad Argentina de Inmunología. SAI-SAIC-SAFIS

Microsporum canis is a dermatophyte fungus that causes superficial infections and is highly prevalent among immunocompetent children. Previously, we demonstrated that M. canis induces a type 17 immunity in vivo that controls fungal proliferation in skin and down-modulates an antigen-specific IFN-γ response.Objective: To evaluate the role of IFN-γ in the experimental dermatophytosis outcome in absence of IL-17RA signaling.Wild type (WT) and IL-17RA-deficient C57BL/6 (KO) mice were epicutaneously infected with M. canis hyphae. On different days post-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) or isotype control (IC) was injected (intraperitoneally) on 3 and 6 dpi. We observed that by 6 and 8 dpi, infected KO showed an increase in fungal burden (p<0,01), neutrophil recruitment (p<0.0001), CXCL1 expression (p<0.05) and TNF (p<0.002) in the skin, compared to WT. After IFN-γ blocking in KO and by 8 dpi, unexpectedly, there was a reduction in fungal burden (p<0.005 vs WT; p<0.05 vs IC treated-KO) with a decrease in neutrophil infiltration (p<0.0001) and TNF production (p<0.001 vs WT, p<0.0001 vs IC-KO). In contrast, these mice showed an increased production of IL-17 pathway-related cytokines 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 epidermal cells.Our results suggest that, in the absence of IL-17 signaling, there is a deregulated Th1 response that promotes M. canis skin infection