title: Listeria monocytogenes induces an interferon-enhanced activation of the integrated stress response that is detrimental for resolution of infection in mice.
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.
authors.affiliation: Division of Immunobiology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.|Department of Microbiology, PhD Biomedical Sciences Program, School of Medicine, Universidad Nacional de Colombia, Bogotá, Colombia.
authors.forename: Carolina
authors.initials: C
authors.lastname: Valderrama
authors.affiliation: Division of Endocrinology, Metabolism and Lipid Research, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Amy
authors.initials: A
authors.lastname: Clark
authors.affiliation: Division of Endocrinology, Metabolism and Lipid Research, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Urano
authors.affiliation: Division of Immunobiology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Emil R
authors.initials: ER
authors.lastname: Unanue
authors.affiliation: Division of Immunobiology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Javier A
authors.identifier: 0000-0001-7712-6160
authors.initials: JA
authors.lastname: Carrero
mesh_terms: D000818:Animals; D001427:Bacterial Toxins / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006460:Hemolysin Proteins / Q000235:genetics / Q000276:immunology; D054884:Host-Pathogen Interactions; D007370:Interferon Type I / Q000096:biosynthesis / Q000276:immunology* / Q000378:metabolism*; D008089:Listeria monocytogenes / Q000276:immunology*; D008088:Listeriosis / Q000276:immunology* / Q000382:microbiology / Q000503:physiopathology; D051379:Mice; D022423:Myeloid Cells / Q000276:immunology* / Q000382:microbiology; D051742:Transcription Factor CHOP / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D000071717:X-Box Binding Protein 1 / Q000235:genetics / Q000378:metabolism; D019892:eIF-2 Kinase / Q000378:metabolism
chemical_list: D001427:Bacterial Toxins; D016207:Cytokines; C497250:Ddit3 protein, mouse; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D006460:Hemolysin Proteins; D007370:Interferon Type I; D000071717:X-Box Binding Protein 1; C000605544:Xbp1 protein, mouse; D051742:Transcription Factor CHOP; D019892:eIF-2 Kinase; C000605978:protein kinase R, mouse; C038705:hlyA protein, Listeria monocytogenes
keywords: CHOP; Integrated stress response; Listeria; Listeriolysin O; Mouse; Type I interferon