Human rhinovirus impairs macrophage innate immune responses to bacteria via the interferon pathway in COPD

Abstract

Introduction: Respiratory viruses are common causes of COPD exacerbations, with human rhinovirus (HRV) being the most frequently identified. Secondary bacterial infection during exacerbation is associated with more severe symptoms, greater airway inflammation and delayed recovery. Alveolar macrophages remove invading pathogens and promote resolution of inflammation, however these processes are defective in COPD Hypothesis: HRV impairs phagocytosis of bacteria by monocyte-derived macrophages (MDM) and alveolar macrophages (AM) in COPD and alters cytokine response to bacteria, delaying bacterial clearance and preventing resolution of inflammation Methods: Participants were recruited from the London COPD cohort. MDM were obtained by adherence from whole blood and AM by bronchoscopy. MDM and AM were infected with HRV16 MOI 5, or exposed to poly I:C 30μg/ml, IFNβ 10μg/ml, IFNγ 10μg/ml or media control for 24 h. Phagocytosis of fluorescently-labelled H.influenzae or S.pneumoniae were assessed by fluorimetry CXCL8 and IL10 release by ELISA Results: HRV16 significantly impaired phagocytosis of H.influenzae by 23% in MDM n=38, 18% in AM n=16 and S. pneumoniae by 33% in MDM n=20 compared to untreated cells. Poly I:C but not IFNβ or IFNγ also impaired phagocytosis of H. influenzae in a concentration dependent manner. HRV16 significantly impaired CXCL8 and IL10 response to H.influenzae. IL10 was significantly reduced by Poly I:C, IFNβ and IFNγ Conclusions: HRV16 impairs phagocytosis of bacteria in MDM and AM in COPD which may lead to an outgrowth of bacteria. HRV also impairs cytokine responses to bacteria via the TLR3/ interferon pathway which may delay recovery from COPD exacerbations