In vivo role of IFN- γ in the skin antifungal response of M. canis infected IL-17RA deficient mice

BURSTEIN V. L.; BECACECCE I.; GUASCONI L.; MENA C.; ORELLANO A.; GRUPPI A.; THEUMER M. G.; CERVI L.; CHIAPELLO L. S.

Congreso; LXIII Reunión Anual de la Sociedad Argentina de Investigación Clínica. LXVI Reunión Científica Anual de la Sociedad Argentina de Inmunología. Reunión Anual de la Sociedad Argentina de Fisiología.; 2018

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 KO C57BL/6 (KO) mice were epicutaneously infected with M. canis hyphae. On different days post-infection (dpi), histopathology, CD11b+Ly6G+ population (neutrophils, FACS) and 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 on 3 and 6 dpi. We observed that by 6 and 8 dpi, infected KO show 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-KO) with a decrease in neutrophil infiltration (p<0,0001) and TNF production (p<0,001 vs WT, p<0,0001 vs IC-KO). However, 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.