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

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.

Serum CYR61 Is Associated With Airway Inflammation and Is a Potential Biomarker for Severity in Chronic Obstructive Pulmonary Disease

“…The mechanism by which CYR61 associates COPD progression remains unclear. Numerous studies demonstrated that chronic airway inflammation aggravated lung function decline in COPD patients (5,29). On the other hand, several studies found that CYR61 had proinflammatory activities (30)(31)(32)(33)(34).…”

Chronic Obstructive Pulmonary Disease Patients Have Increased Levels of Plasma Inflammatory Mediators Reported Upregulated in Severe COVID-19

“…Different viruses are implicated (e.g., rhinovirus, influenza, syncytial respiratory virus and coronavirus), being rhinovirus and coronavirus detected in 35.7% and 25.9% of viral infections occurring during these exacerbations (37). Typically, COPD patients are more susceptible to viral infections; the mechanisms involve dysregulated antiviral function of CD8 + T cells via the PD-1/PD-L1 axis and an altered production of interferons and chemokines (38). Thus, it is possible that the differences in protein plasma levels and their enrichment in viral related pathways observed in this study are the consequences of previous viral infections that induced lung inflammation and alterations on plasma proteome profile.…”

Patients with Asthma and Chronic Obstructive Pulmonary Disease (COPD) have increased levels of plasma inflammatory mediators upregulated in severe COVID-19

“…Typically, COPD patients are more susceptible to viral infections. The mechanisms underlying this susceptibility included dysregulated antiviral function of CD8 + T cells via the PD-1/PD-L1 axis [59] and an altered production of interferons and chemokines [60]. Thus, it is possible that differences in protein plasma levels and the enrichment of differentially expressed proteins in viral related pathways (Figure 4) , could be the consequence of previous viral infections that induced lung inflammation and altered the plasma proteome profile in our COPD patients.…”