title: Pneumococcal hydrogen peroxide-induced stress signaling regulates inflammatory genes.
abstract: Microbial infections can induce aberrant responses in cellular stress pathways, leading to translational attenuation, metabolic restriction, and activation of oxidative stress, with detrimental effects on cell survival. Here we show that infection of human airway epithelial cells with Streptococcus pneumoniae leads to induction of endoplasmic reticulum (ER) and oxidative stress, activation of mitogen-associated protein kinase (MAPK) signaling pathways, and regulation of their respective target genes. We identify pneumococcal H2O2 as the causative agent for these responses, as both catalase-treated and pyruvate oxidase-deficient bacteria lacked these activities. Pneumococcal H2O2 induced nuclear NF-κB translocation and transcription of proinflammatory cytokines. Inhibition of translational arrest and ER stress by salubrinal or of MAPK signaling pathways attenuate cytokine transcription. These results provide strong evidence for the notion that inhibition of translation is an important host pathway in monitoring harmful pathogen-associated activities, thereby enabling differentiation between pathogenic and nonpathogenic bacteria.
authors.affiliation: Institute for Medical Microbiology, German Center for Infection Giessen-Marburg-Langen Site.
authors.forename: Maria
authors.initials: M
authors.lastname: Loose
authors.affiliation: Institute for Medical Microbiology, German Center for Infection Giessen-Marburg-Langen Site.
authors.forename: Martina
authors.initials: M
authors.lastname: Hudel
authors.affiliation: Department of Pediatrics, Justus-Liebig University, Giessen.
authors.forename: Klaus-Peter
authors.initials: KP
authors.lastname: Zimmer
authors.affiliation: Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas, and Centro de Investigación Biomédica en Red de Enfermedades Respiratorias, Madrid, Spain.
authors.forename: Ernesto
authors.initials: E
authors.lastname: Garcia
authors.affiliation: Department Genetics of Microorganisms, Interfaculty Institute for Genetics and Functional Genomics, Ernst Moritz Arndt University of Greifswald, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Hammerschmidt
authors.affiliation: Vascular Biology Center, Department of Pharmacology and Toxicology, Georgia Health Sciences University, Augusta.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Lucas
authors.affiliation: Institute for Medical Microbiology, German Center for Infection Giessen-Marburg-Langen Site.
authors.forename: Trinad
authors.initials: T
authors.lastname: Chakraborty
authors.affiliation: Institute for Medical Microbiology, German Center for Infection Giessen-Marburg-Langen Site.
authors.forename: Helena
authors.initials: H
authors.lastname: Pillich
mesh_terms: D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D004847:Epithelial Cells / Q000276:immunology / Q000382:microbiology; D005786:Gene Expression Regulation / Q000187:drug effects*; D054884:Host-Pathogen Interactions; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D007249:Inflammation; D016328:NF-kappa B / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013296:Streptococcus pneumoniae / Q000276:immunology*; D013312:Stress, Physiological
chemical_list: D016207:Cytokines; D016328:NF-kappa B; D006861:Hydrogen Peroxide
keywords: ER stress; MAPK; Streptococcus pneumonia; hydrogen peroxide; immune response