Regional Differences in Airway Epithelial Cells Reveal Tradeoff between Defense against Oxidative Stress and Defense against Rhinovirus

Cell Rep. 2018 Sep 11;24(11):3000-3007.e3. doi: 10.1016/j.celrep.2018.08.033.

Abstract

Rhinovirus is a leading cause of acute respiratory infections and asthma attacks, but infections are also frequently cleared from the nasal mucosa without causing symptoms. We sought to better understand host defense against rhinovirus by investigating antiviral defense in primary human nasal and bronchial airway epithelial cells cultured ex vivo. Surprisingly, upon rhinovirus infection or RIG-I stimulation, nasal-derived epithelial cells exhibited much more robust antiviral responses than bronchial-derived cells. Conversely, RIG-I stimulation triggered more robust activation of the NRF2-dependent oxidative stress response in bronchial cells compared to nasal cells. NRF2 activation dampened epithelial antiviral responses, whereas NRF2 knockdown enhanced antiviral responses and was protective during rhinovirus infection. These findings demonstrate a tradeoff in epithelial defense against distinct types of airway damage, namely, viral versus oxidative, and reveal differential calibration of defense responses in cells derived from different airway microenvironments.

Keywords: HBEC; HNEC; NRF2; RIG-I; airway epithelial cells; cigarette smoke; innate immunity; oxidative stress; rhinovirus; sulforaphane.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Cells, Cultured
  • Cigarette Smoking / adverse effects
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism*
  • Epithelial Cells / virology*
  • Humans
  • Immunity, Innate / physiology
  • Isothiocyanates / pharmacology
  • NF-E2-Related Factor 2 / metabolism
  • Oxidative Stress / drug effects
  • Oxidative Stress / physiology*
  • Rhinovirus / pathogenicity*

Substances

  • Isothiocyanates
  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • sulforafan