Abstract
BackgroundCampylobacter enteritis represents a risk factor for the development of inflammatory bowel disease (IBD) via unknown mechanisms. As IBD patients exhibit inflammatory responses to their commensal intestinal microflora, factors that induce translocation of commensal bacteria across the intestinal epithelium may contribute to IBD pathogenesis. This study sought to determine whether Campylobacter induces translocation of non-invasive intestinal bacteria, and characterize underlying mechanisms.MethodsMice were infected with C. jejuni and translocation of intestinal bacteria was assessed by quantitative bacterial culture of mesenteric lymph nodes (MLNs), liver, and spleen. To examine mechanisms of Campylobacter-induced bacterial translocation, transwell-grown T84 monolayers were inoculated with non-invasive Escherichia coli HB101 ± wild-type Campylobacter or invasion-defective mutants, and bacterial internalization and translocation were measured. Epithelial permeability was assessed by measuring flux of a 3 kDa dextran probe. The role of lipid rafts was assessed by cholesterol depletion and caveolin co-localization.ResultsC. jejuni 81–176 induced translocation of commensal intestinal bacteria to the MLNs, liver, and spleen of infected mice. In T84 monolayers, Campylobacter-induced internalization and translocation of E. coli occurred via a transcellular pathway, without increasing epithelial permeability, and was blocked by depletion of epithelial plasma membrane cholesterol. Invasion-defective mutants and Campylobacter-conditioned cell culture medium also induced E. coli translocation, indicating that C. jejuni does not directly 'shuttle' bacteria into enterocytes. In C. jejuni-treated monolayers, translocating E. coli associated with lipid rafts, and this phenomenon was blocked by cholesterol depletion.ConclusionCampylobacter, regardless of its own invasiveness, promotes the translocation of non-invasive bacteria across the intestinal epithelium via a lipid raft-mediated transcellular process.
Highlights
Campylobacter enteritis represents a risk factor for the development of inflammatory bowel disease (IBD) via unknown mechanisms
Gut Pathogens 2009, 1:2 http://www.gutpathogens.com/content/1/1/2 may contribute to the development of IBD, as bacteria that translocate through the epithelium may expose submucosal immune cells to inappropriate antigenic stimulation and incite an inflammatory response towards the commensal microflora [2]
C. jejuni induces bacterial translocation of commensal bacteria in vivo Large numbers (P < 0.01) of microaerobic bacteria were isolated from the mesenteric lymph nodes (MLNs), liver, and spleen of C. jejunitreated mice (3.08 ± 0.46, 2.03 ± 0.77, 3.12 ± 0.69 log10 CFU/g, respectively), compared to control mice (0, 0, 0.43 ± 0.43 log10 CFU/g, respectively)
Summary
Campylobacter enteritis represents a risk factor for the development of inflammatory bowel disease (IBD) via unknown mechanisms. As IBD patients exhibit inflammatory responses to their commensal intestinal microflora, factors that induce translocation of commensal bacteria across the intestinal epithelium may contribute to IBD pathogenesis. This study sought to determine whether Campylobacter induces translocation of non-invasive intestinal bacteria, and characterize underlying mechanisms. Patients with IBD appear to display aberrant inflammatory responses to their commensal intestinal microflora via unknown mechanisms [1]. Gut Pathogens 2009, 1:2 http://www.gutpathogens.com/content/1/1/2 may contribute to the development of IBD, as bacteria that translocate through the epithelium may expose submucosal immune cells to inappropriate antigenic stimulation and incite an inflammatory response towards the commensal microflora [2]. Inflammation may become self sustaining due to ineffective down-regulation, despite elimination of the pathogen
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