Listeria monocytogenes induces an interferon‐enhanced activation of the integrated stress response that is detrimental for resolution of infection in mice. Issue 5 (13th April 2017)

• Record Type: Journal Article
• Authors: Valderrama, Carolina; Clark, Amy; Urano, Fumihiko; Unanue, Emil R.; Carrero, Javier A.
• Is Part Of: European journal of immunology. Volume 47:Issue 5(2017)
• Page Start: 830
• Page End: 840
• Publication Date: 2017-04-13
• Subjects: CHOP -- Integrated stress response -- Listeriolysin O -- Listeria -- Mouse -- Type I interferon; Immunology -- Periodicals; 616.079
• DOI: 10.1002/eji.201646856
• Languages: English
• ISSNs: 0014-2980

Abstract

Abstract : Infection with Listeria monocytogenes upregulates CHOP and the integrated stress response in macrophages and dendritic cells. This effect is enhanced by the bacterial toxin listeriolysin O and type I interferon. CHOP‐deficient mice have better early innate immune response and survival than wild‐type mice following Listeria infection. 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.