The dual role of T helper 17-mediated immune response during experimental dermatophytosis

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

Córdoba

Congreso; XIII INFOCUS 2015; 2015

Dermatophytosis is one of the most common superficial mycoses worldwide. It is caused by highly pathogenic keratinophilic fungi that invade the epidermis and cause mild to inflammatory lesions, depending on fungi and host factors. Despite its prevalence, there is not much knowledge about the host inflammatory and immune response to dermatophytes. It is known that a Th1 response is involved in the resolution of the infection however the Th17 response, reported to be crucial not only in barrier defense but also in antifungal response, has not been investigated in the dermatophytosis context yet.The aim of this study was to develop an experimental model of epicutaneous dermatophytosis with Microsporum canis in mice, to characterize the in vivo immune response and to determine the role of interleukin-17 (IL-17) in the antifungal immunity.Wild type (WT) and IL-17RA -/-(KO) C57BL/6 mice were infected with M. canis UNCMc01 hyphae. Histopathological analysis, skin fungal burden (HPLC ergosterol quantification) and extracutaneous fungal dissemination were determined at 4, 8, 18 and 45 days post-infection (d.p.i). Skin draining lymph nodes (sdLN) cells reestimulated in an antigen specific manner and infiltrating cells in skin were analyzed by flow cytometry and their cytokine production by ELISA. T-student test or ANOVA were used for statistical analysis.WT and KO mice developed a superficial mycosis that mimics human tinea that is resolved by 18 d.p.i. and is characterized by a significant increase of neutrophil infiltrate in the skin and IL-17A/F production by CD4 + T cells of sdLN by 8 d.p.i., respect to uninfected mice.Despite IL-17RA KO mice resolved infection, they showed severe Inflammatory skin lesions with a significant higher fungal burden respect to infected WT mice (p<0,0027). They also showed a significant increase in IFN-γ production (p<0,004) in sdLN that was sustained until 45 d.p.i. Although no extracutaneous fungal dissemination was detected, IL-17RA KO mice had a decrease in survival rate.These results are the first to demonstrate the importance of IL-17 in dermatophytosis and that Th17 response has a dual role: controlling antifungal immunity in skin and also restraining the Th1 inflammation-mediated tissue damage of the host. This data allow us to hypothesize that IL-17 could be one of the main host factors that influence inflammation and clinical evolution of skin fungal infections.