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CAMPYLOBACTER JEJUNI INDUCES TRANSLOCATION OF NON-INVASIVE INTESTINAL BACTERIA IN VIVO AND IN VITRO
LD Kalischuk1,2,3, GD Inglis3, AG Buret1,2
1Department of Biological Sciences, 2Inflammation Research Network, University of Calgary, Calgary, Alberta; 3Agriculture and Agri-Food Canada, Lethbridge, Alberta
BACKGROUND: Acute Campylobacter enteritis has been shown to initiate or exacerbate inflammation in patients with inflammatory bowel disease (IBD). It is thought that IBD results, at least in part, from an exaggerated mucosal immune response to intestinal microflora; thus, factors that contribute to increased intestinal bacterial translocation may contribute to the pathogenesis of IBD. As C. jejuni disrupts intestinal epithelial integrity, we hypothesized that C. jejuni facilitates translocation of non-invasive intestinal bacteria.
AIMS: (1) To determine whether C. jejuni causes translocation of non-invasive bacteria across the intestinal epithelial barrier in vivo and in vitro; (2) to characterize the route of epithelial translocation (i.e. paracellular versus transcellular); and (3) to investigate the mechanisms responsible for C. jejuni-induced bacterial translocation.
RESULTS: C. jejuni 81-176 induced translocation of intestinal bacteria (Proteus sp., Acinetobacter sp., Pseudomonas sp.) to the spleens, livers, and mesenteric lymph nodes of infected mice. In human colonic T84 monolayers, C. jejuni induced rapid (4 h) internalization and translocation of non-invasive Escherichia coli HB101 via a transcellular pathway, in the absence of increased epithelial permeability to a FITC-dextran probe (3 kDa). Lipid raft-mediated endocytosis was implicated, as E. coli internalization and translocation were dependent on plasma membrane cholesterol, and were associated with Caveolin-1. C. jejuni invasion was required for bacterial translocation in vivo, as a non-invasive C. jejuni mutant did not induce translocation.
CONCLUSION: The findings indicate that C. jejuni invasion may play an indirect role in bacterial translocation by acting as a cellular stressor, and facilitating lipid raft-mediated uptake of non-invasive intestinal microbes. Increased bacterial translocation coupled with an inflammatory milieu which is present during acute Campylobacter enteritis, may lead to an immunological response to the intestinal microflora, and contribute to the pathogenesis of IBD.