EGFR activation suppresses respiratory virus-induced IRF1-dependent CXCL10 production

April Kalinowski, Iris Ueki, Gundula Min-Oo, Eric Ballon-Landa, David Knoff, Benjamin T. Galen, Lewis L. Lanier, Jay A. Nadel, Jonathan L. Koff

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Airway epithelial cells are the primary cell type involved in respiratory viral infection. Upon infection, airway epithelium plays a critical role in host defense against viral infection by contributing to innate and adaptive immune responses. Influenza A virus, rhinovirus, and respiratory syncytial virus (RSV) represent a broad range of human viral pathogens that cause viral pneumonia and induce exacerbations of asthma and chronic obstructive pulmonary disease. These respiratory viruses induce airway epithelial production of IL-8, which involves epidermal growth factor receptor (EGFR) activation. EGFR activation involves an integrated signaling pathway that includes NADPH oxidase activation of metalloproteinase, and EGFR proligand release that activates EGFR. Because respiratory viruses have been shown to activate EGFR via this signaling pathway in airway epithelium, we investigated the effect of virus-induced EGFR activation on airway epithelial antiviral responses. CXCL10, a chemokine produced by airway epithelial cells in response to respiratory viral infection, contributes to the recruitment of lymphocytes to target and kill virus-infected cells. While respiratory viruses activate EGFR, the interaction between CXCL10 and EGFR signaling pathways is unclear, and the potential for EGFR signaling to suppress CXCL10 has not been explored. Here, we report that respiratory virus-induced EGFR activation suppresses CXCL10 production. We found that influenza virus-, rhinovirus-, and RSV-induced EGFR activation suppressed IFN regulatory factor (IRF) 1-dependent CXCL10 production. In addition, inhibition of EGFR during viral infection augmented IRF1 and CXCL10. These findings describe a novel mechanism that viruses use to suppress endogenous antiviral defenses, and provide potential targets for future therapies.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume307
Issue number2
DOIs
StatePublished - Jul 15 2014
Externally publishedYes

Fingerprint

Epidermal Growth Factor Receptor
Viruses
Virus Diseases
Rhinovirus
Respiratory Syncytial Viruses
Respiratory Tract Infections
Antiviral Agents
Epithelium
Epithelial Cells
Viral Pneumonia
Chemokine CXCL10
NADPH Oxidase
Influenza A virus
Metalloproteases
Adaptive Immunity
Orthomyxoviridae
Interleukin-8
Innate Immunity
Chronic Obstructive Pulmonary Disease
Asthma

Keywords

  • CXCL10
  • Epidermal growth factor receptor
  • Innate immunity
  • Interferon regulatory factor 1

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology
  • Physiology

Cite this

EGFR activation suppresses respiratory virus-induced IRF1-dependent CXCL10 production. / Kalinowski, April; Ueki, Iris; Min-Oo, Gundula; Ballon-Landa, Eric; Knoff, David; Galen, Benjamin T.; Lanier, Lewis L.; Nadel, Jay A.; Koff, Jonathan L.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 307, No. 2, 15.07.2014.

Research output: Contribution to journalArticle

Kalinowski, April ; Ueki, Iris ; Min-Oo, Gundula ; Ballon-Landa, Eric ; Knoff, David ; Galen, Benjamin T. ; Lanier, Lewis L. ; Nadel, Jay A. ; Koff, Jonathan L. / EGFR activation suppresses respiratory virus-induced IRF1-dependent CXCL10 production. In: American Journal of Physiology - Lung Cellular and Molecular Physiology. 2014 ; Vol. 307, No. 2.
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