Mechanisms of Virus-Induced Airway Immunity Dysfunction in the Pathogenesis of COPD Disease, Progression, and Exacerbation

Chronic obstructive pulmonary disease (COPD) is the integrated form of chronic obstructive bronchitis and pulmonary emphysema, characterized by persistent small airway inflammation and progressive irreversible airflow limitation. COPD is characterized by acute pulmonary exacerbations and associated...

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Published inFrontiers in immunology Vol. 11; p. 1205
Main Authors Guo-Parke, Hong, Linden, Dermot, Weldon, Sinéad, Kidney, Joseph C, Taggart, Clifford C
Format Journal Article
LanguageEnglish
Published Switzerland Frontiers Media S.A 16.06.2020
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Abstract Chronic obstructive pulmonary disease (COPD) is the integrated form of chronic obstructive bronchitis and pulmonary emphysema, characterized by persistent small airway inflammation and progressive irreversible airflow limitation. COPD is characterized by acute pulmonary exacerbations and associated accelerated lung function decline, hospitalization, readmission and an increased risk of mortality, leading to huge social-economic burdens. Recent evidence suggests ~50% of COPD acute exacerbations are connected with a range of respiratory viral infections. Nevertheless, respiratory viral infections have been linked to the severity and frequency of exacerbations and virus-induced secondary bacterial infections often result in a synergistic decline of lung function and longer hospitalization. Here, we review current advances in understanding the cellular and molecular mechanisms underlying the pathogenesis of COPD and the increased susceptibility to virus-induced exacerbations and associated immune dysfunction in patients with COPD. The multiple immune regulators and inflammatory signaling pathways known to be involved in host-virus responses are discussed. As respiratory viruses primarily target airway epithelial cells, virus-induced inflammatory responses in airway epithelium are of particular focus. Targeting virus-induced inflammatory pathways in airway epithelial cells such as Toll like receptors (TLRs), interferons, inflammasomes, or direct blockade of virus entry and replication may represent attractive future therapeutic targets with improved efficacy. Elucidation of the cellular and molecular mechanisms of virus infections in COPD pathogenesis will undoubtedly facilitate the development of these potential novel therapies that may attenuate the relentless progression of this heterogeneous and complex disease and reduce morbidity and mortality.
AbstractList Chronic obstructive pulmonary disease (COPD) is the integrated form of chronic obstructive bronchitis and pulmonary emphysema, characterized by persistent small airway inflammation and progressive irreversible airflow limitation. COPD is characterized by acute pulmonary exacerbations and associated accelerated lung function decline, hospitalization, readmission and an increased risk of mortality, leading to huge social-economic burdens. Recent evidence suggests ~50% of COPD acute exacerbations are connected with a range of respiratory viral infections. Nevertheless, respiratory viral infections have been linked to the severity and frequency of exacerbations and virus-induced secondary bacterial infections often result in a synergistic decline of lung function and longer hospitalization. Here, we review current advances in understanding the cellular and molecular mechanisms underlying the pathogenesis of COPD and the increased susceptibility to virus-induced exacerbations and associated immune dysfunction in patients with COPD. The multiple immune regulators and inflammatory signaling pathways known to be involved in host-virus responses are discussed. As respiratory viruses primarily target airway epithelial cells, virus-induced inflammatory responses in airway epithelium are of particular focus. Targeting virus-induced inflammatory pathways in airway epithelial cells such as Toll like receptors (TLRs), interferons, inflammasomes, or direct blockade of virus entry and replication may represent attractive future therapeutic targets with improved efficacy. Elucidation of the cellular and molecular mechanisms of virus infections in COPD pathogenesis will undoubtedly facilitate the development of these potential novel therapies that may attenuate the relentless progression of this heterogeneous and complex disease and reduce morbidity and mortality.
Author Linden, Dermot
Kidney, Joseph C
Taggart, Clifford C
Guo-Parke, Hong
Weldon, Sinéad
AuthorAffiliation 2 Department of Respiratory Medicine Mater Hospital Belfast , Belfast , United Kingdom
1 Airway Innate Immunity Research Group, Wellcome Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry & Biomedical Sciences, Queens University Belfast , Belfast , United Kingdom
AuthorAffiliation_xml – name: 2 Department of Respiratory Medicine Mater Hospital Belfast , Belfast , United Kingdom
– name: 1 Airway Innate Immunity Research Group, Wellcome Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry & Biomedical Sciences, Queens University Belfast , Belfast , United Kingdom
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Copyright Copyright © 2020 Guo-Parke, Linden, Weldon, Kidney and Taggart.
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Keywords acute pulmonary exacerbation
infection
inflammation
virus
chronic obstructive pulmonary disease
lung damage
Language English
License Copyright © 2020 Guo-Parke, Linden, Weldon, Kidney and Taggart.
This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
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These authors share senior authorship
Reviewed by: Giuseppe Lungarella, University of Siena, Italy; Franz Puttur, Imperial College London, United Kingdom
Edited by: Christian Herr, Saarland University Hospital, Germany
This article was submitted to Mucosal Immunity, a section of the journal Frontiers in Immunology
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Snippet Chronic obstructive pulmonary disease (COPD) is the integrated form of chronic obstructive bronchitis and pulmonary emphysema, characterized by persistent...
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StartPage 1205
SubjectTerms acute pulmonary exacerbation
Biomarkers
chronic obstructive pulmonary disease
Disease Progression
Disease Susceptibility - immunology
ErbB Receptors - metabolism
Host-Pathogen Interactions - immunology
Humans
Immunology
infection
Inflammasomes - metabolism
inflammation
Inflammation Mediators - metabolism
lung damage
NF-kappa B - metabolism
Pulmonary Disease, Chronic Obstructive - etiology
Pulmonary Disease, Chronic Obstructive - metabolism
Pulmonary Disease, Chronic Obstructive - pathology
Respiratory Tract Infections - complications
Respiratory Tract Infections - immunology
Signal Transduction
Toll-Like Receptors - metabolism
virus
Virus Diseases - complications
Virus Diseases - immunology
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Title Mechanisms of Virus-Induced Airway Immunity Dysfunction in the Pathogenesis of COPD Disease, Progression, and Exacerbation
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