Department of Dermatology, Jena University Hospital, Jena, Germany.
Department of Urology, Jena University Hospital, Jena, Germany.
J Eur Acad Dermatol Venereol. 2019 Jun;33(6):1177-1188. doi: 10.1111/jdv.15472. Epub 2019 Mar 1.
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).
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.
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.
Trichophyton 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-regulated 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 in 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 keratinocytes, indicating that targeting specific cell-cell adhesion proteins might be part of dermatophytes' virulence strategy.
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.
亲动物性皮肤癣菌须毛癣菌引起的浅表皮肤感染常伴有高度炎症性免疫反应。作为非专业免疫细胞，表皮角质形成细胞和真皮成纤维细胞通过产生促炎细胞因子和抗菌肽 (AMP) 来参与第一道防线。
本研究的目的是更深入地了解发病机制和真菌-宿主相互作用，因为对于这些皮肤细胞对 T. benhamiae 的固有免疫反应知之甚少。
使用与 T. benhamiae DSM 6916 孵育的成纤维细胞和角质形成细胞的皮肤癣菌病模型，分析包括细胞活力和细胞毒性的测定、对固有免疫反应的影响，包括促炎细胞因子/趋化因子的表达和分泌以及 AMP 的表达，以及参与细胞黏附的基因的改变。
T. benhamiae DSM 6916 感染导致严重的细胞损伤，并直接诱导两种皮肤细胞中广泛的促炎细胞因子和趋化因子。只有角质形成细胞在 T. benhamiae DSM 6916 感染后差异地上调 AMP 基因表达。成纤维细胞中 AMP 的表达不能被真菌感染诱导，而它们的缺失可能导致真菌生物量在成纤维细胞中持续增加，而在角质形成细胞中则减少，这可能是由于诱导的 AMP 的抗菌作用。在 mRNA 水平上，T. benhamiae DSM 6916 感染改变了角质形成细胞中的细胞间接触蛋白，表明靶向特定的细胞间黏附蛋白可能是皮肤癣菌毒力策略的一部分。
本研究表明，除了免疫细胞外，角质形成细胞和成纤维细胞也可以参与针对 T. benhamiae DSM 6916 的典型感染的抗菌防御。
