Eukaryotic Initiation Factor 2 (eIF2) signaling regulates proinflammatory cytokine expression and bacterial invasion

Niraj Shrestha, Wael Bahnan, David J. Wiley, Glen N Barber, Kenneth A. Fields, Kurt Schesser

Research output: Contribution to journalArticle

52 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)28738-28744
Number of pages7
JournalJournal of Biological Chemistry
Volume287
Issue number34
DOIs
StatePublished - Aug 17 2012

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Eukaryotic Initiation Factor-2
Cytokines
Pathogens
Bacterial Infections
Yeast
Yeasts
Listeria
Yersinia
Endoplasmic Reticulum Stress
Chlamydia trachomatis
Listeria monocytogenes
Eukaryotic Cells
Virulence Factors
Heavy Metals
Viruses
Antiviral Agents
Toxicity
Chemical activation
Cells

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Eukaryotic Initiation Factor 2 (eIF2) signaling regulates proinflammatory cytokine expression and bacterial invasion. / Shrestha, Niraj; Bahnan, Wael; Wiley, David J.; Barber, Glen N; Fields, Kenneth A.; Schesser, Kurt.

In: Journal of Biological Chemistry, Vol. 287, No. 34, 17.08.2012, p. 28738-28744.

Research output: Contribution to journalArticle

Shrestha, Niraj ; Bahnan, Wael ; Wiley, David J. ; Barber, Glen N ; Fields, Kenneth A. ; Schesser, Kurt. / Eukaryotic Initiation Factor 2 (eIF2) signaling regulates proinflammatory cytokine expression and bacterial invasion. In: Journal of Biological Chemistry. 2012 ; Vol. 287, No. 34. pp. 28738-28744.
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