Abstract
The precise mechanism by which the most common cause of bacterial enterocolitis in humans, Campylobacter jejuni, perturbs the intestinal mucosa remains elusive. To define effects of C. jejuni infection on mucosal permeability, Madin-Darby canine kidney (MDCK)-I and T84 cell monolayers were infected with C. jejuni for up to 48 h. All three tested C. jejuni strains caused a 73–78% reduction in transepithelial electrical resistance (TER) in intestinal (T84) cell monolayers, whereas only one strain slightly reduced TER of MDCK-I cells by 25% after 48 h infection. Infection with C. jejuni strains also caused a 2.3–4.5-fold increase in dextran permeability, but only in T84 cells. C. jejuni infection of monolayers also caused morphologic changes in desmosomes, observed by transmission electron microscopy. The cell-type specificity, demonstrated by increased T84 monolayer permeability, correlated with higher bacterial invasion into these cells, relative to MDCK-I cells. In T84 cells, invasion and bacterial translocation preceded barrier disruption and inhibition of C. jejuni invasion using a pharmacological inhibitor of phosphoinositide 3-kinase, reduced the drop in TER. These findings suggest that C. jejuni disruption of monolayers is mediated by invasion, provide new insights into C. jejuni-host epithelial barrier interactions, and offer potential mechanisms of intestinal injury and chronic immune stimulation.
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Abbreviations
- EHEC:
-
enterohemorrhagic Escherichia coli
- IBD:
-
inflammatory bowel diseases
- MDCK:
-
Madin-Darby canine kidney
- MOI:
-
multiplicity of infection
- PI3-K:
-
phosphoinositide 3-kinase
- TER:
-
transepithelial electrical resistance
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Supported by operating grants from the Canadian Institutes of Health Research (CIHR) and the Crohn's and Colitis Foundation of Canada (Fay Shapiro Cutler Grant in Aid of Research).Supported by a Fellowship Award from the CIHR/Canadian Association of Gastroenterology/AstraZeneca Canada and by a University of Toronto Faculty of Medicine Postgraduate Award (E.W.).PMS is the recipient of a Canada Research Chair in Gastrointestinal Disease.
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Wine, E., Chan, V. & Sherman, P. Campylobacter jejuni Mediated Disruption of Polarized Epithelial Monolayers is Cell-Type Specific, Time Dependent, and Correlates With Bacterial Invasion. Pediatr Res 64, 599–604 (2008). https://doi.org/10.1203/PDR.0b013e31818702b9
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DOI: https://doi.org/10.1203/PDR.0b013e31818702b9
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