Abstract
Campylobacter jejuni invasion is closely related to C. jejuni pathogenicity. The intestinal epithelium contains polarized epithelial cells that form tight junctions (TJs) to provide a physical barrier against bacterial invasion. Previous studies indicated that C. jejuni invasion of non-polarized cells involves several cellular features, including lipid rafts. However, the dynamics of C. jejuni invasion of polarized epithelial cells are not fully understood. Here we investigated the interaction between C. jejuni invasion and TJ formation to characterize the mechanism of C. jejuni invasion in polarized epithelial cells. In contrast to non-polarized epithelial cells, C. jejuni invasion was not affected by depletion of lipid rafts in polarized epithelial cells. However, depletion of lipid rafts significantly decreased C. jejuni invasion in TJ disrupted cells or basolateral infection and repair of cellular TJs suppressed lipid raft-mediated C. jejuni invasion in polarized epithelial cells. In addition, pro-inflammatory cytokine, TNF-α treatment that induce TJ disruption promote C. jejuni invasion and lipid rafts depletion significantly reduced C. jejuni invasion in TNF-α treated cells. These data demonstrated that TJs prevent C. jejuni invasion from the lateral side of epithelial cells, where they play a main part in bacterial invasion and suggest that C. jejuni invasion could be increased in inflammatory condition. Therefore, maintenance of TJs integrity should be considered important in the development of novel therapies for C. jejuni infection.
Highlights
Campylobacter jejuni is a Gram-negative, spiral-shaped, microaerophilic bacterium that is found in birds and domestic animals
U18666A treatment of INT407 cells significantly decreased C. jejuni invasion without affecting the cholesterol content (Figures 1E,F). Together these results indicated that cell surface cholesterol and lipid rafts are essential for C. jejuni invasion of non-polarized epithelial cells
We examined whether tight junctions (TJs) could prevent C. jejuni invasion by comparing C. jejuni invasion of polarized and non-polarized cells under a variety of treatments to disrupt TJs
Summary
Campylobacter jejuni is a Gram-negative, spiral-shaped, microaerophilic bacterium that is found in birds and domestic animals. C. jejuni causes human bacterial food-borne diseases worldwide, and clinical symptoms are manifested as intestinal inflammation, abdominal pain, and diarrhea (Young et al, 2007). IL8 production recruit neutrophils to the infection site and subsequently host inflammatory responses to C. jejuni infection. The mutant C. jejuni strains lacking invasion activity had attenuated inflammatory responses and several diarrhea symptoms in experimental animal models (Yao et al, 1997). Together these findings indicate that bacterial invasion into host intestinal epithelial cells plays a critical role in C. jejuni pathogenicity
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