Immune-Mediated Aggravation of the <i>Campylobacter concisus</i>-Induced Epithelial Barrier Dysfunction

• Main Authors: Praveen Kumar Nattramilarasu, Fábia Daniela Lobo de Sá, Jörg-Dieter Schulzke, Roland Bücker
• Format: Article
• Language: English
• Published: MDPI AG 2021-02-01
• Series: International Journal of Molecular Sciences
• Subjects: <i>Campylobacter concisus</i>; HT-29/B6-GR/MR cells; THP-1 cells; leaky gut model; tricellular tight junction; tricellulin
• Online Access: https://www.mdpi.com/1422-0067/22/4/2043
• ISSN: 1661-6596; 1422-0067

<i>Campylobacter concisus</i> is a human-pathogenic bacterium of the gastrointestinal tract. This study aimed at the contribution of the mucosal immune system in the context of intestinal epithelial barrier dysfunction induced by <i>C. concisus</i>. As an experimental leaky gut model, we used in vitro co-cultures of colonic epithelial cell monolayers (HT-29/B6-GR/MR) with M1-macrophage-like THP-1 cells on the basal side. Forty-eight hours after <i>C. concisus</i> infection, the decrease in the transepithelial electrical resistance in cell monolayers was more pronounced in co-culture condition and 22 ± 2% (<i>p</i> < 0.001) higher than the monoculture condition without THP-1 cells. Concomitantly, we observed a reduction in the expression of the tight junction proteins occludin and tricellulin. We also detected a profound increase in 4 kDa FITC-dextran permeability in <i>C. concisus</i>-infected cell monolayers only in co-culture conditions. This is explained by loss of tricellulin from tricellular tight junctions (tTJs) after <i>C. concisus</i> infection. As an underlying mechanism, we observed an inflammatory response after <i>C. concisus</i> infection through pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) released from THP-1 cells in the co-culture condition. In conclusion, the activation of subepithelial immune cells exacerbates colonic epithelial barrier dysfunction by <i>C. concisus</i> through tricellulin disruption in tTJs, leading to increased antigen permeability (leaky gut concept).