Expression of fungal and host markers in a relevant mouse model of dermatophytosis

Dermatophytoses are the most common skin mycoses affecting humans and animals worldwide. The increasing resistance of dermatophytes to antifungal agents is creating a serious public health problem, and it is therefore essential to better understand the pathogenesis of dermatophytosis. Dermatophytes can switch from a saprophytic to a parasitic lifestyle by reprogramming their gene expression, as has been demonstrated for Trichophyton benhamiae in guinea pigs, so reliable animal models are still needed. Our aim was to develop a relevant mouse model of T. benhamiae dermatophytosis to study host-fungus relationship. The use of a specific standardized fungal mixture of spores, germ tubes and mycelium as inoculum induced a natural-type superficial infection in mice, with hyphae invading the epidermis and inflammatory epidermal and dermal infiltration of mononuclear and polymorphonuclear cells. The severity and persistence of the lesions, as well as the optimization of the extraction method for murine and fungal RNA recovery, enabled the expression of infection markers to be assessed. While infection induces early overexpression of mouse-specific pro-inflammatory genes, several fungal genes are also overexpressed, including those encoding certain subtilisins (SUB) previously reported as potential virulence factors, such as SUB3 and SUB6. Some SUB are also overexpressed during in vitro infection on reconstructed human epidermis and may represent common robust fungal markers of dermatophyte infection across all potential hosts. Therefore, our mouse model appears to be a good analytical tool for studying the pathophysiology of acute dermatophytoses.