Regional Differences in Airway Epithelial Cells Reveal Tradeoff between Defense against Oxidative Stress and Defense against Rhinovirus
Summary: 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 nas...
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doaj-09a058a5867f4819817f0ea560f28f4b2020-11-24T21:53:26ZengElsevierCell Reports2211-12472018-09-01241130003007.e3Regional Differences in Airway Epithelial Cells Reveal Tradeoff between Defense against Oxidative Stress and Defense against RhinovirusValia T. Mihaylova0Yong Kong1Olga Fedorova2Lokesh Sharma3Charles S. Dela Cruz4Anna Marie Pyle5Akiko Iwasaki6Ellen F. Foxman7Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT 06520, USADepartment of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USAHoward Hughes Medical Institute, New Haven, CT 06520, USADepartment of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USADepartment of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USADepartment of Molecular, Cellular and Developmental Biology and Department of Chemistry, Yale University, New Haven, CT 06520, USA; Howard Hughes Medical Institute, New Haven, CT 06520, USADepartment of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA; Howard Hughes Medical Institute, New Haven, CT 06520, USADepartment of Laboratory Medicine, Yale University School of Medicine, New Haven, CT 06520, USA; Corresponding authorSummary: 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. : Airway epithelial cells form the first line of defense against harmful substances that enter the airway. Mihaylova et al. show that viral RNA detection triggers both the NRF2-mediated oxidative stress response and the antiviral interferon response in epithelial cells and demonstrates a tradeoff between these defense responses. Keywords: rhinovirus, NRF2, RIG-I, innate immunity, oxidative stress, airway epithelial cells, HNEC, HBEC, cigarette smoke, sulforaphanehttp://www.sciencedirect.com/science/article/pii/S2211124718313044 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Valia T. Mihaylova Yong Kong Olga Fedorova Lokesh Sharma Charles S. Dela Cruz Anna Marie Pyle Akiko Iwasaki Ellen F. Foxman |
spellingShingle |
Valia T. Mihaylova Yong Kong Olga Fedorova Lokesh Sharma Charles S. Dela Cruz Anna Marie Pyle Akiko Iwasaki Ellen F. Foxman Regional Differences in Airway Epithelial Cells Reveal Tradeoff between Defense against Oxidative Stress and Defense against Rhinovirus Cell Reports |
author_facet |
Valia T. Mihaylova Yong Kong Olga Fedorova Lokesh Sharma Charles S. Dela Cruz Anna Marie Pyle Akiko Iwasaki Ellen F. Foxman |
author_sort |
Valia T. Mihaylova |
title |
Regional Differences in Airway Epithelial Cells Reveal Tradeoff between Defense against Oxidative Stress and Defense against Rhinovirus |
title_short |
Regional Differences in Airway Epithelial Cells Reveal Tradeoff between Defense against Oxidative Stress and Defense against Rhinovirus |
title_full |
Regional Differences in Airway Epithelial Cells Reveal Tradeoff between Defense against Oxidative Stress and Defense against Rhinovirus |
title_fullStr |
Regional Differences in Airway Epithelial Cells Reveal Tradeoff between Defense against Oxidative Stress and Defense against Rhinovirus |
title_full_unstemmed |
Regional Differences in Airway Epithelial Cells Reveal Tradeoff between Defense against Oxidative Stress and Defense against Rhinovirus |
title_sort |
regional differences in airway epithelial cells reveal tradeoff between defense against oxidative stress and defense against rhinovirus |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2018-09-01 |
description |
Summary: 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. : Airway epithelial cells form the first line of defense against harmful substances that enter the airway. Mihaylova et al. show that viral RNA detection triggers both the NRF2-mediated oxidative stress response and the antiviral interferon response in epithelial cells and demonstrates a tradeoff between these defense responses. Keywords: rhinovirus, NRF2, RIG-I, innate immunity, oxidative stress, airway epithelial cells, HNEC, HBEC, cigarette smoke, sulforaphane |
url |
http://www.sciencedirect.com/science/article/pii/S2211124718313044 |
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