Yersinia pseudotuberculosis disrupts intestinal barrier integrity through hematopoietic TLR-2 signaling
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
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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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 9

Y. pseudotuberculosis increases MLCK expression.

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Y. pseudotuberculosis increases MLCK expression. (A) WT, Il1r–/–, and...
(A) WT, Il1r–/–, and Tlr2–/– mice were inoculated i.g. with pIB102, then killed 5 days after infection. PPs were removed, and mRNA expression of MLCK was determined by real-time PCR. n = 8 per group; 3 independent experiments. ***P < 0.001 versus uninfected WT; ††P < 0.01 versus pIB102-infected WT. (B) PPs from chimeric mice were removed and incubated for 6 hours with pIB102 in UCs, after which mRNA expression of MLCK was determined by real-time PCR. n = 6 per group; 2 independent experiments. #P < 0.05 versus pIB102-infected +/+ → +/+. (C and D) Caco-2 cells were cultivated into TCs, infected THP-1 cells were added into the TC basolateral compartment, and (B) mRNA expression and (C) protein level of MLCK were investigated after 24 hours of incubation. n ≥ 8 per group; 3 independent experiments. *P < 0.05, ***P < 0.001 versus uninfected THP-1; ††P < 0.01, †††P < 0.001 versus pIB102-infected THP-1.