Listeria monocytogenes induces an interferon-enhanced activation of the integrated stress response that is detrimental for resolution of infection in mice

Carolina Valderrama, Amy Clark, Fumihiko Urano, Emil R. Unanue, Javier A. Carrero

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Type I interferons (IFNs) induce a detrimental response during Listeria monocytogenes (L. monocytogenes) infection. We were interested in identifying mechanisms linking IFN signaling to negative host responses against L. monocytogenes infection. Herein, we found that infection of myeloid cells with L. monocytogenes led to a coordinated induction of type I IFNs and activation of the integrated stress response (ISR). Infected cells did not induce Xbp1 splicing or BiP upregulation, indicating that the unfolded protein response was not triggered. CHOP (Ddit3) gene expression was upregulated during the ISR activation induced by L. monocytogenes. Myeloid cells deficient in either type I IFN signaling or PKR activation had less upregulation of CHOP following infection. CHOP-deficient mice showed lower expression of innate immune cytokines and were more resistant than wild-type counterparts following L. monocytogenes infection. These findings indicate that L. monocytogenes infection induces type I IFNs, which activate the ISR through PKR, which contributes to a detrimental outcome in the infected host.

Original languageEnglish
Pages (from-to)830-840
Number of pages11
JournalEuropean Journal of Immunology
Volume47
Issue number5
DOIs
StatePublished - May 2017

Keywords

  • CHOP
  • Integrated stress response
  • Listeria
  • Listeriolysin O
  • Mouse
  • Type I interferon

Fingerprint Dive into the research topics of 'Listeria monocytogenes induces an interferon-enhanced activation of the integrated stress response that is detrimental for resolution of infection in mice'. Together they form a unique fingerprint.

  • Cite this