Pneumococcal hydrogen peroxide-induced stress signaling regulates inflammatory genes

Maria Loose, Martina Hudel, Klaus Peter Zimmer, Ernesto Garcia, Sven Hammerschmidt, Rudolf Lucas, Trinad Chakraborty, Helena Pillich

Research output: Contribution to journalArticle

15 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)306-316
Number of pages11
JournalJournal of Infectious Diseases
Volume211
Issue number2
DOIs
StatePublished - Jan 15 2015

Keywords

  • ER stress
  • MAPK
  • Streptococcus pneumonia
  • hydrogen peroxide
  • immune response

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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  • Cite this

    Loose, M., Hudel, M., Zimmer, K. P., Garcia, E., Hammerschmidt, S., Lucas, R., Chakraborty, T., & Pillich, H. (2015). Pneumococcal hydrogen peroxide-induced stress signaling regulates inflammatory genes. Journal of Infectious Diseases, 211(2), 306-316. https://doi.org/10.1093/infdis/jiu428