Campylobacter jejuni Mediated Disruption of Polarized Epithelial Monolayers is Cell-Type Specific, Time Dependent, and Correlates With Bacterial Invasion

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. (Pediatr Res 64: 599-604, 2008)

Pathogenesis of Human Enterovirulent Bacteria: Lessons from Cultured, Fully Differentiated Human Colon Cancer Cell Lines

“…When infecting the basolateral domain, C. jejuni causes a more rapid decrease in TER but a comparable redistribution of TJ proteins (657). Internalization of C. jejuni into fully differentiated T84 cells through a phosphoinositide 3-kinase (PI3K)-dependent mechanism is accompanied by a reduction of TER (658).…”

Campylobacter Jejuni Increases Transcribed Il-1 B and Causes Morphometric Changes in the Ileal Enterocytes of Chickens

“…In vitro, the inoculation of C. jejuni in the cell monolayer has been shown to increase paracellular permeability and the transepithelial flux of the cultured cells (LambRosteski et al, 2008). Additionally, C. jejuni disrupts intercellular junctions, increasing the width of the infected cells compared with the controls (Wine, Chan, & Sherman, 2008). Cytolethal Distending Toxin (CDT) induces a cytoplasmic distension and leads to cell death (Jeon, Itoh, & Ryu, 2005).…”

A Glance at Prokaryotes and Eukaryotes Interplay and Campylobacter jejuni–Host Interaction

“…Studies of the translocation capabilities of C. jejuni strains across an intestinal epithelium in vitro require tight polarized cell monolayers. Typical chosen cell lines expressing TJs, AJs and FAs include Caco-2, T84, MDCK-I or MKN-28 (Konkel et al 1992a, b;Everest et al 1993;Grant et al 1993;Harvey et al 1999;Monteville and Konkel 2002;Chen et al 2006;Hu et al 2008;Wine et al 2008;Boehm et al 2012;Hoy et al 2012;). …”

“…1999;Beltinger et al 2008;Wine et al 2008;. It was proposed that C. jejuni can enter cultured epithelial cell lines of human origin with higher efficacy as compared to non-human cells, suggesting that the pathogen is particularly specialized for disease triggering infection of the human host (Konkel et al 1992a, b;.…”