Innate immune response of human epidermal keratinocytes and dermal fibroblast to in vitro incubation of Trichophyton benhamiae DSM 6916.

BACKGROUND: Superficial cutaneous infection caused by the zoophilic dermatophyte Trichophyton benhamiae is often associated with a highly inflammatory immune response. As non-professional immune cells, epidermal keratinocytes and dermal fibroblasts contribute to the first line of defence by producing pro-inflammatory cytokines and antimicrobial peptides (AMP).

OBJECTIVE: Purpose of this study was to gain a deeper understanding of the pathogenesis and the fungal-host interaction as not much is known about the innate immune response of these cutaneous cells against T. benhamiae.

METHODS: Using a dermatophytosis model of fibroblasts and keratinocytes incubated with T. benhamiae DSM 6916, analyses included determination of cell-viability and cytotoxicity, effects on the innate immune response including expression and secretion of pro-inflammatory cytokines/ chemokines and expression of AMP, as well as alterations of genes involved in cell adhesion.

RESULTS: T. benhamiae DSM 6916 infection led to severe cell damage and direct induction of a broad spectrum of pro-inflammatory cytokines and chemokines in both cutaneous cells. Only keratinocytes differentially up-regulate AMP genes expression after T. benhamiae DSM 6916 infection. Expression of AMPs in fibroblasts was not inducible by fungal infection, whereas their absences potentially contributed to a continuous increase of the fungal biomass on fibroblasts, which in turn was reduced in keratinocytes possibly due to the antimicrobial actions of induced AMPs. On mRNA level, T. benhamiae DSM 6916 infection altered cell-cell-contact proteins in keratinocyte, indicating that targeting specific cell-cell adhesion proteins might be part of dermatophytes' virulence strategy.

CONCLUSION: This study showed that in addition to immune cells, keratinocytes and fibroblasts could participate in antimicrobial defence against an exemplary infection with T. benhamiae DSM 6916. This article is protected by copyright. All rights reserved.