Yersinia pseudotuberculosis disrupts intestinal barrier integrity through hematopoietic TLR-2 signaling
Camille Jung, … , Jean-Pierre Hugot, Frederick Barreau
Camille Jung, … , Jean-Pierre Hugot, Frederick Barreau
Published May 8, 2012
Citation Information: J Clin Invest. 2012;122(6):2239-2251. https://doi.org/10.1172/JCI58147.
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Research Article Gastroenterology

Yersinia pseudotuberculosis disrupts intestinal barrier integrity through hematopoietic TLR-2 signaling

Abstract

Intestinal barrier function requires intricate cooperation between intestinal epithelial cells and immune cells. Enteropathogens are able to invade the intestinal lymphoid tissue known as Peyer’s patches (PPs) and disrupt the integrity of the intestinal barrier. However, the underlying molecular mechanisms of this process are poorly understood. In mice infected with Yersinia pseudotuberculosis, we found that PP barrier dysfunction is dependent on the Yersinia virulence plasmid and the expression of TLR-2 by hematopoietic cells, but not by intestinal epithelial cells. Upon TLR-2 stimulation, Y. pseudotuberculosis–infected monocytes activated caspase-1 and produced IL-1β. In turn, IL-1β increased NF-κB and myosin light chain kinase activation in intestinal epithelial cells, thus disrupting the intestinal barrier by opening the tight junctions. Therefore, Y. pseudotuberculosis subverts intestinal barrier function by altering the interplay between immune and epithelial cells during infection.

Authors

Camille Jung, Ulrich Meinzer, Nicolas Montcuquet, Elodie Thachil, Danielle Château, Raphaële Thiébaut, Maryline Roy, Ziad Alnabhani, Dominique Berrebi, Monique Dussaillant, Eric Pedruzzi, Sophie Thenet, Nadine Cerf-Bensussan, Jean-Pierre Hugot, Frederick Barreau

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Figure 7

IL-1β secreted by Y. pseudotuberculosis–infected THP-1 cells alters paracellular permeability and E. coli translocation across Caco-2 monolayers.

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IL-1β secreted by Y. pseudotuberculosis–infected THP-1 cells alters para...
(A) Caco-2 and (B) Caco-2 clone-1 cells were cultivated into TCs. Then, THP-1 cells infected or not with pIB102 were added to the TC basolateral compartment, and (A) paracellular permeability and (B) E. coli translocation were monitored. To investigate the involvement of IL-1β receptor, Caco-2 and Caco-2 clone-1 cells were treated for 24 hours with anakinra (50 μg/ml). n ≥ 10 per group; 3 independent experiments. ***P < 0.001 versus basal (–); †††P < 0.001 versus pIB102-infected THP-1. (C and D) TJ width of Caco-2 cells incubated with infected THP-1 cells was measured by EM. Scale bars: 100 nm. n = 150 measures of TJs per group from 3 independent wells. ***P < 0.001 versus uninfected THP-1. (E) Apical distribution of occludin and ZO-1 of Caco-2 cells incubated with infected THP-1 cells was analyzed by confocal microscopy. Scale bar: 20 μm. (F) Western blot analysis of occludin in Caco-2 cells incubated with infected THP-1 cells. n = 3 per group. **P < 0.01 versus uninfected THP-1.