Role of γδT cells in skin homeostasis and protective immunity during experimental dermatophytosis

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Human fungal diseases continue to represent a major global health problem, in particular in children, in the elderly and in immune-deficient individuals. In recent decades, our understanding of the molecular pathways that control innate recognition of fungi and antifungal responses elicited by myeloid cells has significantly improved. However, we still understand less about organ-specific adaptive immune responses and cytokine networks that control fungal growth. Dermatophytoses are skin infections caused by keratinophilic filamentous fungi affecting approximately 25% of the world population, thereby representing the fourth most prevalent cause of human disease. Despite this enormous incidence, disease pathogenesis and host responses to dermatophytes are scarcely investigated in comparison to other fungal infections. Here, the Argentinean and German partners will jointly investigate the skin’s immune responses to dermatophytosis and address how commensal bacteria and pathogenic fungi drive skin immune homeostasis. Innate γδT lymphocytes are emerging as central players in skin immunity against pathogens as well as in maintaining homeostasis with commensal microorganisms. Therefore, we will monitor their antifungal functions against dermatophytes in an experimental model of epicutaneous infection with Microsporum spp., which mimics human dermatomycosis. Specifically, we will investigate the role of dermal γδT cells that produce the pro-inflammatory cytokine interleukin-17-producing in response to dermatophyte infection. Furthermore, we will study the microbial and metabolic factors that modulate immune homeostasis between interleukin-17-producing immune cells and pathogenic or commensal fungi of the skin. This proposal outlines a highly collaborative and complementary research project that will mutually benefit the laboratories of Dr. Laura Chiapello (CIBICI-CONICET) and Dr. Immo Prinz (Institute of Immunology, Hannover, Germany). The Argentine group provides experience in the management of pathogenic fungi and experimental infections, and the German group is experienced in γδT cell biology and the in vivo study of immune cell dynamics in tissues.