Campylobacter jejuni induces transcytosis of commensal bacteria across the intestinal epithelium through M-like cells

Abstract

BackgroundRecent epidemiological analyses have implicated acute Campylobacter enteritis as a factor that may incite or exacerbate inflammatory bowel disease (IBD) in susceptible individuals. We have demonstrated previously that C. jejuni disrupts the intestinal barrier function by rapidly inducing epithelial translocation of non-invasive commensal bacteria via a transcellular lipid raft-mediated mechanism ('transcytosis'). To further characterize this mechanism, the aim of this current study was to elucidate whether C. jejuni utilizes M cells to facilitate transcytosis of commensal intestinal bacteria.ResultsC. jejuni induced translocation of non-invasive E. coli across confluent Caco-2 epithelial monolayers in the absence of disrupted transepithelial electrical resistance or increased permeability to a 3 kDa dextran probe. C. jejuni-infected monolayers displayed increased numbers of cells expressing the M cell-specific marker, galectin-9, reduced numbers of enterocytes that stained with the absorptive enterocyte marker, Ulex europaeus agglutinin-1, and reduced activities of enzymes typically associated with absorptive enterocytes (namely alkaline phosphatase, lactase, and sucrase). Furthermore, in Campylobacter-infected monolayers, E. coli were observed to be internalized specifically within epithelial cells displaying M-like cell characteristics.ConclusionThese data indicate that C. jejuni may utilize M cells to promote transcytosis of non-invasive bacteria across the intact intestinal epithelial barrier. This mechanism may contribute to the inflammatory immune responses against commensal intestinal bacteria commonly observed in IBD patients.

Campylobacter jejuni Translocation across Intestinal Epithelial Cells Is Facilitated by Ganglioside-Like Lipooligosaccharide Structures

“…In line with previous studies (22,26,45), our data also provide support for a transcytosis-mediated model for C. jejuni translocation across host epithelia, including apical endocytosis and basolateral exocytosis.…”

Gastrointestinal infection as a trigger for inflammatory bowel disease

“…The prevalence of Campylobacter jejuni and other species, including C. concisus, is higher in patients with IBD than non-IBD controls; in one study of pediatric Crohn's disease [8], the prevalence by genus-specific PCR was 72% in fecal samples from children with Crohn's disease, significantly different than the 30% observed in healthy and non-IBD controls (Table 1). Although the significance of these findings in relation to causation of IBD is unknown, it has recently been demonstrated in vitro that C. jejuni infection can promote the transport of commensal bacteria across an intact intestinal epithelial monolayer, and so may contribute to persistent inflammation seen in individuals with IBD [28]. In a recent study of a population-based cohort [29], individuals with exposure to Salmonella or Campylobacter gastroenteritis (based on stool culture) and no concurrent diagnosis of IBD were identified.…”

Commensal bacterial internalization by epithelial cells: An alternative portal for gut leakiness

“…34,35 These studies have shown that depletion of membranous cholesterol by cholesterol-sequestering agents (methyl-b-cyclodextrin or filipin) and gene silencing of caveolin-1 abolished endocytosis and transcytosis of nonpathogenic bacteria by epithelial cells in in vitro models after IFNg treatment 15,38 and C. jejuni infection. 45,46 Moreover, caveolin-1 or cholesterol was found colocalized with bacteria-containing endosomes in epithelial cells. 15,45 Invasive pathogens (e.g., Salmonella spp., Shigella spp, and enterohemorrhagic or enteroinvasive Escherichia coli) use their needle-like type III secretion systems to inject effector proteins into epithelial cells, and subsequently manipulate the host cytoskeletal actins for anchorage and entry.…”

“…[44][45][46] The lumen-dwelling G. lamblia causes diffuse microvilli shortening, TJ disruption and epithelial cell apoptosis, 47,48 that may partly contribute to bacterial penetration. Moreover, it has been reported that intracellular C. jejuni-containing vacuoles deviate from the canonical endosomal pathways, avoiding delivery into lysosomes.…”