Inflammatory Bowel Diseases

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Inflammatory Bowel Diseases:
doi: 10.1002/ibd.20325
Original Basic Science Articles: Campylobacter and IFN[gamma]: Original Article

Campylobacterand IFNγ interact to cause a rapid loss of epithelial barrier integrity

Rees, Louisa E.N. PhD1; Cogan, Tristan A. PhD1,*; Dodson, Amanda L. BSc1; Birchall, Martin A. MD1; Bailey, Mick PhD1; Humphrey, Tom J. PhD1

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Background:: The intestinal epithelium is a single layer of polarized cells and is the primary barrier separating foreign antigen and underlying lymphoid tissue. IFNγ alters epithelial barrier function during inflammation by disrupting tight cell junctions and facilitating the paracellular transport of luminal antigens. The aim of this work was to determine whether Campylobacter infection of cells exposed to IFNγ would lead to greater disruption of cell monolayers and hence increased bacterial translocation.

Methods:: Monolayers were polarized on Transwell polycarbonate membranes for 14 days and then cultured in the presence or absence of 100 U/mL IFNγ. Campylobacter was added to the apical side of the monolayer at an MOI of 30. Transepithelial electrical resistance (TEER) was recorded and bacteria in the basal well counted every 2 hours. Cells were stained for occludin, actin, and nuclear DNA, and cell viability determined by measurement of apoptosis.

Results:: In the presence of IFNγ, TEER dropped significantly after 18 hours, indicating a reduction in barrier function. A further significant decrease was seen in the presence of both IFNγ and Campylobacter, indicating a synergistic effect, and cellular morphology and viability were affected. Bacterial translocation across the monolayer was also significantly greater in the presence of IFNγ.

Conclusions:: These combined effects indicate that Campylobacter infection concomitant with intestinal inflammation would result in a rapid and dramatic loss of epithelial barrier integrity, which may be a key event in the pathogenesis of Campylobacter‐mediated colitis and the development of bloody diarrhea.

© Crohn's & Colitis Foundation of America, Inc.

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