ArticleRespiratory research2016
Human primary airway epithelial cells isolated from active smokers have epigenetically impaired antiviral responses.
Article in Respiratory research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 46 citations in OpenAlex.
- Epigenetic dysregulation of IRF9 drives excessive interferon signaling in COPD.EMBO molecular medicine · 2026Article
- LncRNA GAS5 attenuates COPD pathogenesis by stabilizing p120 catenin to suppress NF-κB-driven inflammation.Respiratory research · 2025Article
- A translational view of airway epithelial dysfunction in COPD.European respiratory review : an official journal of the European Respiratory Society · 2025Review
- CYP1B1 knockout enhanced IFN-γ production is required but not sufficient for protection of cigarette smoke-exposed mice against lethal influenza virus infection.Frontiers in immunology · 2025Article
- Interleukin 13-Induced Inflammation Increases DPP4 Abundance but Does Not Enhance Middle East Respiratory Syndrome Coronavirus Replication in Airway Epithelia.The Journal of infectious diseases · 2024Article
- Cigarette smoke sustains immunosuppressive microenvironment inducing M2 macrophage polarization and viability in lung cancer settings.PloS one · 2024Article
- RIG-I agonist SLR10 promotes macrophage M1 polarization during influenza virus infection.Frontiers in immunology · 2023Article
- In Vivo and In Vitro Studies of Cigarette Smoke Effects on Innate Responses to Influenza Virus: A Matter of Models?Viruses · 2022Review
- Cigarette Smoke Extract Disturbs Mitochondria-Regulated Airway Epithelial Cell Responses to Pneumococci.Cells · 2022Article
- Lung epithelial cells interact with immune cells and bacteria to shape the microenvironment in tuberculosis.Thorax · 2022Review
- Deciphering Respiratory-Virus-Associated Interferon Signaling in COPD Airway Epithelium.Medicina (Kaunas, Lithuania) · 2022Review
- Altered Differentiation and Inflammation Profiles Contribute to Enhanced Innate Responses in Severe COPD Epithelium to Rhinovirus Infection.Frontiers in medicine · 2022Article
- Smoking and COVID-19: The Real Deal.Annals of the American Thoracic Society · 2021Article
- In Vitro Models for Studying Respiratory Host-Pathogen Interactions.Advanced biology · 2021Review
- Long-term cigarette smoke exposure dysregulates pulmonary T cell response and IFN-γ protection to influenza virus in mouse.Respiratory research · 2021Article
- Influenza in High-Risk Hosts-Lessons Learned from Animal Models.Cold Spring Harbor perspectives in medicine · 2020Review
- Article
- FluA-p score: a novel prediction rule for mortality in influenza A-related pneumonia patients.Respiratory research · 2020Article
- Interferon therapy for preventing COPD exacerbations.EXCLI journal · 2020Article
- Cigarette Smoke Affects Dendritic Cell Populations, Epithelial Barrier Function, and the Immune Response to Viral Infection With H1N1.Frontiers in medicine · 2020Article
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 1 country.
Funding
Abstract
backgroundCigarette smoking (CS) is the main risk factor for the development of chronic obstructive pulmonary disease (COPD) and most COPD exacerbations are caused by respiratory infections including influenza. Influenza infections are more severe in smokers. The mechanism of the increased risk and severity of infections in smokers is likely multifactorial, but certainly includes changes in immunologic host defenses.
methodsWe investigated retinoic acid-inducible protein I (RIG-I) and interferon (IFN) induction by influenza A virus (IAV) in human bronchial epithelial cells (HBEC) isolated from smokers or nonsmokers. Subcultured HBEC cells were infected with A/Puerto Rico/8/1934 (PR8) IAV at an MOI of 1. After 24 h of infection, cells and supernatants were collected for qRT-PCR, immunoblot or ELISA to determine RIG-I, Toll-like receptor3 (TLR3) and IFN expression levels.
resultsIAV exposure induced a vigorous IFN-β, IFN-λ 1 and IFN-λ 2/3 antiviral response in HBEC from nonsmokers and significant induction of RIG-I and TLR3. In cells from smokers, viral RIG-I and TLR3 mRNA induction was reduced 87 and 79 % compared to the response from nonsmokers. CS exposure history was associated with inhibition of viral induction of the IFN-β, IFN-λ1 and IFN-λ 2/3 mRNA response by 85, 96 and 95 %, respectively, from that seen in HBEC from nonsmokers. The demethylating agent 5-Aza-2-deoxycytidine reversed the immunosuppressive effects of CS exposure in HBEC since viral induction of all three IFNs was restored. IFN-β induction of RIG-I and TLR3 was also suppressed in the cells from smokers.
conclusionOur results suggest that active smoking reduces expression of antiviral cytokines in primary HBEC cells. This effect likely occurs via downregulation of RIG-I and TLR3 due to smoke-induced epigenetic modifications. Reduction in lung epithelial cell RIG-I and TLR3 responses may be a major mechanism contributing to the increased risk and severity of viral respiratory infections in smokers and to viral-mediated acute exacerbations of COPD.
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Registered trials
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