Vitamin D Reverses Disruption of Gut Epithelial Barrier Function Caused by Campylobacter jejuni

作者：Fábia Daniela Lobo de Sá, Steffen Backert, Praveen Kumar Nattramilarasu, Soraya Mousavi, Geoffrey I. Sandle, Stefan Bereswill, Markus M. Heimesaat, Jörg–Dieter Schulzke, Roland Bücker · 发表于：International Journal of Molecular Sciences · 年份：2021 · DOI：10.3390/ijms22168872 · 被引用次数：23 · 研究领域：Clostridium difficile and Clostridium perfringens research、Barrier Structure and Function Studies、Trace Elements in Health

Infections by the zoonotic foodborne bacterium Campylobacter jejuni (C. jejuni) are among the most frequent causes of bacterial gastroenteritis worldwide. The aim was to evaluate the relationship between epithelial barrier disruption, mucosal immune activation, and vitamin D (VD) treatment during C. jejuni infection, using intestinal epithelial cells and mouse models focused on the interaction of C. jejuni with the VD signaling pathway and VD treatment to improve C. jejuni-induced barrier dysfunction. Our RNA-Seq data from campylobacteriosis patients demonstrate inhibition of VD receptor (VDR) downstream targets, consistent with suppression of immune function. Barrier-preserving effects of VD addition were identified in C. jejuni-infected epithelial cells and IL-10−/− mice. Furthermore, interference of C. jejuni with the VDR pathway was shown via VDR/retinoid X receptor (RXR) interaction. Paracellular leakiness of infected epithelia correlated with tight junction (TJ) protein redistribution off the TJ domain and apoptosis induction. Supplementation with VD reversed barrier impairment and prevented inhibition of the VDR pathway, as shown by restoration of transepithelial electrical resistance and fluorescein (332 Da) permeability. We conclude that VD treatment restores gut epithelial barrier functionality and decreases bacterial transmigration and might, therefore, be a promising compound for C. jejuni treatment in humans and animals.