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

14 Citations (Scopus)

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 H 2 O 2 as the causative agent for these responses, as both catalase-treated and pyruvate oxidase-deficient bacteria lacked these activities. Pneumococcal H 2 O 2 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

Fingerprint

Endoplasmic Reticulum Stress
Mitogens
Protein Kinases
Hydrogen Peroxide
Pyruvate Oxidase
Oxidative Stress
Cytokines
Bacteria
Streptococcus pneumoniae
Infection
Catalase
Genes
Cell Survival
Epithelial Cells
salubrinal
Metabolic Activation

Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

Cite this

Loose, M., Hudel, M., Zimmer, K. P., Garcia, E., Hammerschmidt, S., Lucas, R., ... 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

Pneumococcal hydrogen peroxide-induced stress signaling regulates inflammatory genes. / Loose, Maria; Hudel, Martina; Zimmer, Klaus Peter; Garcia, Ernesto; Hammerschmidt, Sven; Lucas, Rudolf; Chakraborty, Trinad; Pillich, Helena.

In: Journal of Infectious Diseases, Vol. 211, No. 2, 15.01.2015, p. 306-316.

Research output: Contribution to journalArticle

Loose, M, Hudel, M, Zimmer, KP, Garcia, E, Hammerschmidt, S, Lucas, R, Chakraborty, T & Pillich, H 2015, 'Pneumococcal hydrogen peroxide-induced stress signaling regulates inflammatory genes', Journal of Infectious Diseases, vol. 211, no. 2, pp. 306-316. https://doi.org/10.1093/infdis/jiu428
Loose, Maria ; Hudel, Martina ; Zimmer, Klaus Peter ; Garcia, Ernesto ; Hammerschmidt, Sven ; Lucas, Rudolf ; Chakraborty, Trinad ; Pillich, Helena. / Pneumococcal hydrogen peroxide-induced stress signaling regulates inflammatory genes. In: Journal of Infectious Diseases. 2015 ; Vol. 211, No. 2. pp. 306-316.
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