Skin immunity: IL-17 protects against epidermal dermatophytic infection and regulates the exacerbated inflammatory antifungal response

BURSTEIN VL; THEUMER MG; GUASCONI L; HERRERO M; MENA C; MASIH DT; CHIAPELLO L S

Buenos Aires

Encuentro; IV LASID Meeting. LXII Argentinean Immunology Society Meeting. II French-Argentinean Immunology Meeting; 2015

Sociedad Argentina de Inmunología

Microsporum canis is a zoophilic dermatophytic that causes contagious skin infections with mild to severe inflammatory lesions, highly prevalent in immunocompetent children. Our previous data demonstrate that epicutaneous infection of C57BL/6 mice with M. canis is characterized by a Th17 response, however the in vivo role of IL-17 signaling has not been demonstrated. The aim of this study was to evaluate the impact of IL-17 in the outcome of skin infection and the antifungal inflammatory response.Wild type (WT) and IL-17RA-/- (KO) C57BL/6 mice were epicutaneously infected with M.canis and at 4, 8, 18 and 45 days post-infection (d.p.i)histopathological analysis, skin fungal burden (HPLC ergosterol quantification) and extracutaneous fungal disseminationwere determined. CD11b+ and T CD4+, T CD8+, Tγdelta and B cell populations and its cytokine production were analyzed (ELISA or intracellular staining and FACS) in skin cell suspensions or in skin draining lymph nodes cells (sdLN) after antigen specific-reestimulation. In addition, survival rate was registered. WT and KO mice resolved infection by 18 d.p.i., however KO mice showed severe inflammatory response in skin and sdLNs (p<0,004), with a higher skin fungal burden than infected WT (p<0,003). KO also showed an increase in IFN-γ (p<0,004) production by T CD4+ sdLN cells that was sustained until 45 d.p.i. Despite extracutaneous fungal dissemination was not detected, KO mice had a decrease in survival rate.These results demonstrate that IL-17RA signaling controls the epidermal dermatophytic invasion and also suggest a main role in regulating Th1-mediated inflammation.