title: Yersinia pseudotuberculosis effector YopJ subverts the Nod2/RICK/TAK1 pathway and activates caspase-1 to induce intestinal barrier dysfunction.
abstract: Yersinia pseudotuberculosis is an enteropathogenic bacteria that disrupts the intestinal barrier and invades its host through gut-associated lymphoid tissue and Peyer's patches (PP). We show that the Y. pseudotuberculosis effector YopJ induces intestinal barrier dysfunction by subverting signaling of the innate immune receptor Nod2, a phenotype that can be reversed by pretreating with the Nod2 ligand muramyl-dipeptide. YopJ, but not the catalytically inactive mutant YopJ(C172A), acetylates critical sites in the activation loops of the RICK and TAK1 kinases, which are central mediators of Nod2 signaling, and decreases the affinity of Nod2 for RICK. Concomitantly, Nod2 interacts with and activates caspase-1, resulting in increased levels of IL-1β. Finally, IL-1β within PP plays an essential role in inducing intestinal barrier dysfunction. Thus, YopJ alters intestinal permeability and promotes the dissemination of Yersinia as well as commensal bacteria by exploiting the mucosal inflammatory response.
authors.affiliation: Université Paris-Diderot, Paris, France.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Meinzer
authors.forename: Frederick
authors.initials: F
authors.lastname: Barreau
authors.forename: Sophie
authors.initials: S
authors.lastname: Esmiol-Welterlin
authors.forename: Camille
authors.initials: C
authors.lastname: Jung
authors.forename: Claude
authors.initials: C
authors.lastname: Villard
authors.forename: Thibaut
authors.initials: T
authors.lastname: Léger
authors.forename: Sanah
authors.initials: S
authors.lastname: Ben-Mkaddem
authors.forename: Dominique
authors.initials: D
authors.lastname: Berrebi
authors.forename: Monique
authors.initials: M
authors.lastname: Dussaillant
authors.forename: Ziad
authors.initials: Z
authors.lastname: Alnabhani
authors.forename: Maryline
authors.initials: M
authors.lastname: Roy
authors.forename: Stéphane
authors.initials: S
authors.lastname: Bonacorsi
authors.forename: Hans
authors.initials: H
authors.lastname: Wolf-Watz
authors.forename: Julie
authors.initials: J
authors.lastname: Perroy
authors.forename: Vincent
authors.initials: V
authors.lastname: Ollendorff
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Hugot
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D020170:Caspase 1 / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000201:enzymology* / Q000382:microbiology; D020930:MAP Kinase Kinase Kinases / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics / Q000378:metabolism*; D053475:Receptor-Interacting Protein Serine-Threonine Kinase 2 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D015011:Yersinia pseudotuberculosis / Q000235:genetics / Q000378:metabolism*; D015012:Yersinia pseudotuberculosis Infections / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism / Q000382:microbiology; D000099151:MAP Kinase Kinase Kinase 7
chemical_list: D001426:Bacterial Proteins; D020170:Caspase 1; D020930:MAP Kinase Kinase Kinases; D053473:Nod2 Signaling Adaptor Protein; D053475:Receptor-Interacting Protein Serine-Threonine Kinase 2; D000099151:MAP Kinase Kinase Kinase 7; C109227:YopP protein, Yersinia