title: Eukaryotic initiation factor 2 (eIF2) signaling regulates proinflammatory cytokine expression and bacterial invasion.
abstract: In eukaryotic cells, there are two well characterized pathways that regulate translation initiation in response to stress, and each have been shown to be targeted by various viruses. We recently showed in a yeast-based model that the bacterial virulence factor YopJ disrupts one of these pathways, which is centered on the α-subunit of the translation factor eIF2. Here, we show in mammalian cells that induction of the eIF2 signaling pathway occurs following infection with bacterial pathogens and that, consistent with our yeast-based findings, YopJ reduces eIF2 signaling in response to endoplasmic reticulum stress, heavy metal toxicity, dsRNA, and bacterial infection. We demonstrate that the well documented activities of YopJ, inhibition of NF-κB activation and proinflammatory cytokine expression, are both dependent on an intact eIF2 signaling pathway. Unexpectedly, we found that cells with defective eIF2 signaling were more susceptible to bacterial invasion. This was true for pathogenic Yersinia, a facultative intracellular pathogen, as well as for the intracellular pathogens Listeria monocytogenes and Chlamydia trachomatis. Collectively, our data indicate that the highly conserved eIF2 signaling pathway, which is vitally important for antiviral responses, plays a variety of heretofore unrecognized roles in antibacterial responses.
authors: Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, Florida 33136, USA.
authors: Niraj
authors: N
authors: Shrestha
authors: Wael
authors: W
authors: Bahnan
authors: David J
authors: DJ
authors: Wiley
authors: Glen
authors: G
authors: Barber
authors: Kenneth A
authors: KA
authors: Fields
authors: Kurt
authors: K
authors: Schesser
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D002690:Chlamydia Infections / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002692:Chlamydia trachomatis / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D015852:Eukaryotic Initiation Factor-2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism*; D008089:Listeria monocytogenes / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008088:Listeriosis / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction; D015007:Yersinia / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015009:Yersinia Infections / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D016207:Cytokines; D015852:Eukaryotic Initiation Factor-2; D018836:Inflammation Mediators; D016328:NF-kappa B; C109227:YopP protein, Yersinia