Rationale
Human rhinovirus (HRV) is a common cause of COPD exacerbations. Some patients with COPD experience frequent exacerbations. The biological mechanisms underlying exacerbation frequency are unknown.
Interferons are produced by alveolar macrophages and bronchial epithelial cells (BECS), limiting viral replication. The role of interferons in COPD remains controversial.
Secondary bacterial infection is also common. Alveolar macrophages clear bacteria from the lung. The effect of HRV on macrophage function is unknown.
Hypotheses
IFN responses to HRV are impaired in BECS and alveolar macrophages from COPD patients compared to healthy subjects.
In patients with frequent exacerbations, IFN responses will be further impaired leading to increased exacerbation frequency.
HRV impairs phagocytosis of bacteria in macrophages from COPD subjects increasing risk of secondary bacterial infection.
Methods
Alveolar macrophages and BECS were obtained by bronchoscopy from COPD patients and healthy controls. Alveolar macrophages and BECS were infected with HRV16 or medium for 24 hours. IFNs and proinflammatory were measured in supernatants by meso-scale discovery (MSD).
Macrophages and MDM were exposed to HRV or medium for 24 hours. Phagocytosis of fluorescently labelled bacteria was assessed by fluorimetry.
Main Results
IFN responses to HRV16 were significantly impaired in alveolar macrophages but not BECS from patients with COPD compared to healthy controls.
IFN-β response to HRV16 was significantly reduced in BECS and alveolar macrophages from frequent exacerbators compared to infrequent exacerbators.
HRV significantly impaired phagocytosis of bacteria by in MDM and alveolar macrophages in COPD. There was no effect in healthy controls.
Conclusions
IFN response to HRV was impaired in alveolar macrophages from COPD patients and further impaired in patients with frequent exacerbations. HRV impaired phagocytosis of bacteria in alveolar macrophages in COPD which may lead to an outgrowth of bacteria. These findings suggest an impaired anti-viral response may drive increased risk of frequent exacerbations in COPD.