Human Rhinovirus Impairs the Innate Immune Response to Bacteria in Alveolar Macrophages in Chronic Obstructive Pulmonary Disease

Human rhinovirus (HRV) is a common cause of chronic obstructive pulmonary disease (COPD) exacerbations. Secondary bacterial infection is associated with more severe symptoms and delayed recovery. Alveolar macrophages clear bacteria from the lung and maintain lung homeostasis through cytokine secretion. These processes are defective in COPD. The effect of HRV on macrophage function is unknown. To investigate the effect of HRV on phagocytosis and cytokine response to bacteria by alveolar macrophages and monocyte-derived macrophages (MDM) in COPD and healthy control subjects. Alveolar macrophages were obtained by bronchoscopy and MDM by adherence. Macrophages were exposed to HRV16 (multiplicity of infection 5), polyinosinic:polycytidylic acid (poly I:C) 30 μg/ml, IFN-β 10 μg/ml, IFN-γ 10 μg/ml, or medium control for 24 hours. Phagocytosis of fluorescently labeled or was assessed by fluorimetry. CXCL8 (IL-8), IL-6, TNF-α (tumor necrosis factor-α), and IL-10 release was measured by ELISA. HRV significantly impaired phagocytosis of by 23% in MDM ( = 37;  = 0.004) and 18% in alveolar macrophages ( = 20;  < 0.0001) in COPD. HRV also significantly reduced phagocytosis of by 33% in COPD MDM ( = 20;  = 0.0192). There was no effect in healthy control subjects. Phagocytosis of was also impaired by poly I:C but not IFN-β or IFN-γ in COPD MDM. HRV significantly reduced cytokine responses to . The IL-10 response to was significantly impaired by poly I:C, IFN-β, and IFN-γ in COPD cells. HRV impairs phagocytosis of bacteria in COPD, which may lead to an outgrowth of bacteria. HRV also impairs cytokine responses to bacteria via the TLR3/IFN pathway, which may prevent resolution of inflammation leading to prolonged exacerbations in COPD.