Optimisation of a Murine Infection Model With Trichophyton mentagrophytes for Studying the Pathogenesis of Dermatophytosis.

Abstract

BACKGROUND: Dermatophytes are the most common agents of superficial mycoses in humans and animals. In a model of Trichophyton benhamiae dermatophytosis in its natural host (guinea pig), the most overexpressed gene was subtilisin 6 (SUB6). Given the availability of powerful genetic and immunological tools in mice, murine models of dermatophytosis should be developed using strains that can mimic natural infections. OBJECTIVE: The aim of this study was to test a strain of Trichophyton mentagrophytes isolated from a rodent in a murine skin infection model, to characterise the expression of key host and fungal genes and investigate the role of SUB6 in virulence by mimicking a natural infection as closely as possible. RESULTS: A phylogenetic tree was generated to better discriminate the T. mentagrophytes strains isolated from animals. The T. mentagrophytes TIMM 2789 strain used in this study is genotype IV, specific to rodents. Infection induced symptoms and lesions, including hair follicle invasion, typical of acute superficial dermatophytosis. Early overexpression of genes encoding specific cytokines revealed the involvement of the Th1, Th2 and Th17 responses by the host, and the overexpression of the fungal SIDC gene underscores the importance of iron acquisition during infection. The use of deleted and complemented SUB6 strains revealed that SUB6 does not appear to be necessary for fungal virulence, while SUB5 overexpression suggests a compensatory mechanism. CONCLUSION: This study demonstrates the crucial importance of carefully selecting the most appropriate dermatophyte strain for the animal species in the experimental model used.