title: 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.affiliation: Université Paris-Diderot, UMR843, Paris, France.
authors.forename: Camille
authors.initials: C
authors.lastname: Jung
authors.forename: Ulrich
authors.initials: U
authors.lastname: Meinzer
authors.forename: Nicolas
authors.initials: N
authors.lastname: Montcuquet
authors.forename: Elodie
authors.initials: E
authors.lastname: Thachil
authors.forename: Danielle
authors.initials: D
authors.lastname: Château
authors.forename: Raphaële
authors.initials: R
authors.lastname: Thiébaut
authors.forename: Maryline
authors.initials: M
authors.lastname: Roy
authors.forename: Ziad
authors.initials: Z
authors.lastname: Alnabhani
authors.forename: Dominique
authors.initials: D
authors.lastname: Berrebi
authors.forename: Monique
authors.initials: M
authors.lastname: Dussaillant
authors.forename: Eric
authors.initials: E
authors.lastname: Pedruzzi
authors.forename: Sophie
authors.initials: S
authors.lastname: Thenet
authors.forename: Nadine
authors.initials: N
authors.lastname: Cerf-Bensussan
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Hugot
authors.forename: Frederick
authors.initials: F
authors.lastname: Barreau
mesh_terms: D000818:Animals; D018938:Caco-2 Cells; D020170:Caspase 1 / Q000235:genetics / Q000276:immunology; D004789:Enzyme Activation / Q000235:genetics / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics / Q000276:immunology; D007413:Intestinal Mucosa / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009000:Monocytes / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D009219:Myosin-Light-Chain Kinase / Q000235:genetics / Q000276:immunology; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology; D010581:Peyer's Patches / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000276:immunology*; D015011:Yersinia pseudotuberculosis / Q000235:genetics / Q000276:immunology*; D015012:Yersinia pseudotuberculosis Infections / Q000235:genetics / Q000276:immunology* / Q000473:pathology
chemical_list: D053583:Interleukin-1beta; D016328:NF-kappa B; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D009219:Myosin-Light-Chain Kinase; D020170:Caspase 1