Yersinia pseudotuberculosis disrupts intestinal barrier integrity through hematopoietic TLR-2 signaling |
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Authors: | Jung Camille Meinzer Ulrich Montcuquet Nicolas Thachil Elodie Château Danielle Thiébaut Raphaële Roy Maryline Alnabhani Ziad Berrebi Dominique Dussaillant Monique Pedruzzi Eric Thenet Sophie Cerf-Bensussan Nadine Hugot Jean-Pierre Barreau Frederick |
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Affiliation: | Université Paris-Diderot, UMR843, Paris, France. |
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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. |
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