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 LS

Congreso; LASID IV Meeting Argentina; 2015

Microsporum canis is a zoophilic dermatophytic that causes contagious skin infectionswith mild to severe inflammatory lesions, highly prevalent in immunocompetent children. Our previousdata demonstrate that epicutaneous infection of C57BL/6 mice with M. canis is characterized by a Th17response, 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 theantifungal 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 ergosterolquantification) and extracutaneous fungal dissemination were determined. CD11b+ and T CD4+, TCD8+, Tγ� and B cell populations and its cytokine production were analyzed (ELISA or intracellularstaining and FACS) in skin cell suspensions or in skin draining lymph nodes cells (sdLN) after antigenspecific-reestimulation. In addition, survival rate was registered.WT and KO mice resolved infection by 18 d.p.i., however KO mice showed severe inflammatoryresponse in skin and sdLNs (p<0,004), with a higher skin fungal burden than infected WT (p<0,003). KOalso showed an increase in IFN-γ (p<0,004) production by T CD4+ sdLN cells that was sustained until45 d.p.i. Despite extracutaneous fungal dissemination was not detected, KO mice had a decrease insurvival rate.These results demonstrate that IL-17 RA signaling controls the epidermal dermatophytic invasion andalso suggest a main role in regulating Th1-mediated inflammation.Ethics Committee: NO