title: Proinflammatory signalling stimulated by the type III translocation factor YopB is counteracted by multiple effectors in epithelial cells infected with Yersinia pseudotuberculosis.
abstract: Type III secretion systems are used by several pathogens to translocate effector proteins into host cells. Yersinia pseudotuberculosis delivers several Yop effectors (e.g. YopH, YopE and YopJ) to counteract signalling responses during infection. YopB, YopD and LcrV are components of the translocation machinery. Here, we demonstrate that a type III translocation protein stimulates proinflammatory signalling in host cells, and that multiple effector Yops counteract this response. To examine proinflammatory signalling by the type III translocation machinery, HeLa cells infected with wild-type or Yop-Y. pseudotuberculosis strains were assayed for interleukin (IL)-8 production. HeLa cells infected with a YopEHJ- triple mutant released significantly more IL-8 than HeLa cells infected with isogenic wild-type, YopE-, YopH- or YopJ- bacteria. Complementation analysis demonstrated that YopE, YopH or YopJ are sufficient to counteract IL-8 production. IL-8 production required YopB, but did not require YopD, pore formation or invasin-mediated adhesion. In addition, YopB was required for activation of nuclear factor kappa B, the mitogen-activated protein kinases ERK and JNK and the small GTPase Ras in HeLa cells infected with the YopEHJ- mutant. We conclude that interaction of the Yersinia type III translocator factor YopB with the host cell triggers a proinflammatory signalling response that is counteracted by multiple effectors in host cells.
authors.affiliation: Department of Molecular Genetics and Microbiology, Center for Infectious Diseases, School of Medicine, State University of New York at Stony Brook, Stony Brook, NY 11794-5222, USA.
authors.forename: Gloria I
authors.initials: GI
authors.lastname: Viboud
authors.forename: Stephane Shu Kin
authors.initials: SS
authors.lastname: So
authors.forename: Michelle B
authors.initials: MB
authors.lastname: Ryndak
authors.forename: James B
authors.initials: JB
authors.lastname: Bliska
mesh_terms: D000942:Antigens, Bacterial / Q000502:physiology*; D001425:Bacterial Outer Membrane Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology*; D004789:Enzyme Activation; D005786:Gene Expression Regulation; D005816:Genetic Complementation Test; D006367:HeLa Cells; D006801:Humans; D007249:Inflammation; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics; D048031:JNK Mitogen-Activated Protein Kinases; D020935:MAP Kinase Signaling System; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D052899:Pore Forming Cytotoxic Proteins; D021381:Protein Transport / Q000235:genetics / Q000502:physiology*; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000502:physiology*; D014774:Virulence; D015011:Yersinia pseudotuberculosis / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D018631:ras Proteins / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism
chemical_list: D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D016209:Interleukin-8; C043908:LcrV protein, Yersinia; D016328:NF-kappa B; D009363:Neoplasm Proteins; D052899:Pore Forming Cytotoxic Proteins; C078909:YopB protein, Yersinia; C109227:YopP protein, Yersinia; C063239:yopE protein, Yersinia; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D017027:Protein Tyrosine Phosphatases; C067571:yopH protein, Yersinia; D018631:ras Proteins; D020741:rho GTP-Binding Proteins