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 10

Y. pseudotuberculosis disrupts epithelial barrier functions by modulating MLCK activity.

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Y. pseudotuberculosis disrupts epithelial barrier functions by modulati...
(A and B) WT mice were treated i.p. with ML-7 (2 mg/kg), ML-9 (2 mg/kg), or peptide 18 (P18; 100 μg/mouse) for 2 consecutive days before experimentation. PPs from treated WT mice were then mounted in UCs and incubated with pIB102, and (A) paracellular permeability and (B) bacterial translocation of E. coli K-12 were monitored. n ≥ 8 per group; 3 independent experiments. ***P < 0.001 versus uninfected WT; ††P < 0.01, †††P < 0.001 versus pIB102-infected WT. (C and D) Caco-2 (C) and Caco-2 clone-1 (D) cells were cultivated into TCs. After 24 hours of ML-7 or ML-9 (50 μg/ml) treatment, infected THP-1 cells were added into the TC basolateral compartment, and (C) paracellular permeability and (D) E. coli translocation were monitored. n ≥ 8 per group; 3 independent experiments. ***P < 0.001 versus uninfected THP-1; ††P < 0.01, †††P < 0.001 versus pIB102-infected THP-1. (E) MLCK activity was assessed by measuring phosphorylation of MLC (MLC-P) in Caco-2 cells by Western blot analyses. A representative blot of 3 independent experiments is shown.