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Deciphering Respiratory-Virus-Associated Interferon Signaling in COPD Airway Epithelium

COPD is a chronic lung disorder characterized by a progressive and irreversible airflow obstruction, and persistent pulmonary inflammation. It has become a global epidemic affecting 10% of the population, and is the third leading cause of death worldwide. Respiratory viruses are a primary cause of C...

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Autores principales: Guo-Parke, Hong, Linden, Dermot, Weldon, Sinéad, Kidney, Joseph C., Taggart, Clifford C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8781535/
https://www.ncbi.nlm.nih.gov/pubmed/35056429
http://dx.doi.org/10.3390/medicina58010121
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author Guo-Parke, Hong
Linden, Dermot
Weldon, Sinéad
Kidney, Joseph C.
Taggart, Clifford C.
author_facet Guo-Parke, Hong
Linden, Dermot
Weldon, Sinéad
Kidney, Joseph C.
Taggart, Clifford C.
author_sort Guo-Parke, Hong
collection PubMed
description COPD is a chronic lung disorder characterized by a progressive and irreversible airflow obstruction, and persistent pulmonary inflammation. It has become a global epidemic affecting 10% of the population, and is the third leading cause of death worldwide. Respiratory viruses are a primary cause of COPD exacerbations, often leading to secondary bacterial infections in the lower respiratory tract. COPD patients are more susceptible to viral infections and associated severe disease, leading to accelerated lung function deterioration, hospitalization, and an increased risk of mortality. The airway epithelium plays an essential role in maintaining immune homeostasis, and orchestrates the innate and adaptive responses of the lung against inhaled and pathogen insults. A healthy airway epithelium acts as the first line of host defense by maintaining barrier integrity and the mucociliary escalator, secreting an array of inflammatory mediators, and initiating an antiviral state through the interferon (IFN) response. The airway epithelium is a major site of viral infection, and the interaction between respiratory viruses and airway epithelial cells activates host defense mechanisms, resulting in rapid virus clearance. As such, the production of IFNs and the activation of IFN signaling cascades directly contributes to host defense against viral infections and subsequent innate and adaptive immunity. However, the COPD airway epithelium exhibits an altered antiviral response, leading to enhanced susceptibility to severe disease and impaired IFN signaling. Despite decades of research, there is no effective antiviral therapy for COPD patients. Herein, we review current insights into understanding the mechanisms of viral evasion and host IFN antiviral defense signaling impairment in COPD airway epithelium. Understanding how antiviral mechanisms operate in COPD exacerbations will facilitate the discovery of potential therapeutic interventions to reduce COPD hospitalization and disease severity.
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spelling pubmed-87815352022-01-22 Deciphering Respiratory-Virus-Associated Interferon Signaling in COPD Airway Epithelium Guo-Parke, Hong Linden, Dermot Weldon, Sinéad Kidney, Joseph C. Taggart, Clifford C. Medicina (Kaunas) Review COPD is a chronic lung disorder characterized by a progressive and irreversible airflow obstruction, and persistent pulmonary inflammation. It has become a global epidemic affecting 10% of the population, and is the third leading cause of death worldwide. Respiratory viruses are a primary cause of COPD exacerbations, often leading to secondary bacterial infections in the lower respiratory tract. COPD patients are more susceptible to viral infections and associated severe disease, leading to accelerated lung function deterioration, hospitalization, and an increased risk of mortality. The airway epithelium plays an essential role in maintaining immune homeostasis, and orchestrates the innate and adaptive responses of the lung against inhaled and pathogen insults. A healthy airway epithelium acts as the first line of host defense by maintaining barrier integrity and the mucociliary escalator, secreting an array of inflammatory mediators, and initiating an antiviral state through the interferon (IFN) response. The airway epithelium is a major site of viral infection, and the interaction between respiratory viruses and airway epithelial cells activates host defense mechanisms, resulting in rapid virus clearance. As such, the production of IFNs and the activation of IFN signaling cascades directly contributes to host defense against viral infections and subsequent innate and adaptive immunity. However, the COPD airway epithelium exhibits an altered antiviral response, leading to enhanced susceptibility to severe disease and impaired IFN signaling. Despite decades of research, there is no effective antiviral therapy for COPD patients. Herein, we review current insights into understanding the mechanisms of viral evasion and host IFN antiviral defense signaling impairment in COPD airway epithelium. Understanding how antiviral mechanisms operate in COPD exacerbations will facilitate the discovery of potential therapeutic interventions to reduce COPD hospitalization and disease severity. MDPI 2022-01-13 /pmc/articles/PMC8781535/ /pubmed/35056429 http://dx.doi.org/10.3390/medicina58010121 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Guo-Parke, Hong
Linden, Dermot
Weldon, Sinéad
Kidney, Joseph C.
Taggart, Clifford C.
Deciphering Respiratory-Virus-Associated Interferon Signaling in COPD Airway Epithelium
title Deciphering Respiratory-Virus-Associated Interferon Signaling in COPD Airway Epithelium
title_full Deciphering Respiratory-Virus-Associated Interferon Signaling in COPD Airway Epithelium
title_fullStr Deciphering Respiratory-Virus-Associated Interferon Signaling in COPD Airway Epithelium
title_full_unstemmed Deciphering Respiratory-Virus-Associated Interferon Signaling in COPD Airway Epithelium
title_short Deciphering Respiratory-Virus-Associated Interferon Signaling in COPD Airway Epithelium
title_sort deciphering respiratory-virus-associated interferon signaling in copd airway epithelium
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8781535/
https://www.ncbi.nlm.nih.gov/pubmed/35056429
http://dx.doi.org/10.3390/medicina58010121
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