Abstract
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.
Highlights
Chronic obstructive pulmonary disease (COPD) is a common chronic inflammatory airways disease affecting 1.2 million people in the UK, and 10% of the global population aged over 45 [1]
The airway epithelium plays an essential role in maintaining immune homeostasis, and modulating the innate and adaptive immune response in the lung against inhaled and pathogen insults [4]
Induction of type I and type III interferon antiviral responses have been demonstrated for several respiratory viruses via the interaction of retinoic acid-inducible gene I (RIG-I)/melanoma differentiation-associated gene 5 (MDA5), caspase activation and recruitment domain (CARD), and their adaptor proteins mitochondrial antiviral-signaling protein (MAVS), IFN-β promoter stimulator 1 (IPS-1), leading to activation of downstream NF-κB and IFN regulatory factors (IRFs)-3 pathways [14,15,36,37,38]
Summary
Chronic obstructive pulmonary disease (COPD) is a common chronic inflammatory airways disease affecting 1.2 million people in the UK, and 10% of the global population aged over 45 [1]. As a primary site of respiratory viral infection, airway epithelial cells act as the first line of host defense by maintaining barrier integrity and the mucociliary escalator to prevent virus binding and entry into the host [3,4]. It initiates the innate and adaptive immune response by secreting an array of inflammatory mediators, such as cytokines, chemokines, growth factors, lipid mediators, inflammasomes, and proteases [3,5,6]. We highlight current advances in understanding mechanisms of how respiratory viruses modulate or evade these antiviral defenses
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