Impaired anti-viral immunity in frequent exacerbators of chronic obstructive pulmonary disease.

Abstract

Background Respiratory viruses cause chronic obstructive pulmonary disease (COPD) exacerbations. Rhinoviruses (RVs) are the most frequently detected. Some COPD patients experience frequent exacerbations ({greater than or equal to}2 exacerbations/ year). The relationship between exacerbation frequency and anti-viral immunity remains poorly understood. Objectives To investigate the relationship between exacerbation frequency and anti-viral immunity in COPD Methods Alveolar macrophages and bronchial epithelial cells (BECs) were obtained from COPD patients and healthy participants. Alveolar macrophages were infected with RV-A16 multiplicity of infection 5 (MOI 5) and BECs infected with RV-A16 MOI 1 for 24 hours. Interferons (IFN) and pro-inflammatory cytokines IL-1β, IL-6, CXCL8 and TNF were measured in cell supernatants using mesoscale discovery platform. Viral load and interferon stimulated genes were measured in cell lysates using qPCR. Results Spontaneous and RV induced IFN-β, IFN-γ and CXCL-11 release were significantly reduced in alveolar macrophages from COPD patients compared to healthy subjects. IFN-β was further impaired in uninfected alveolar macrophages from COPD patients with frequent exacerbations 82.0 pg/mL vs infrequent exacerbators 234.7 pg/mL P=0.008 and RV-infected alveolar macrophages from frequent exacerbators 158.1 pg/mL vs infrequent exacerbators 279.5 pg/mL P=0.022. Release of proinflammatory cytokines CXCL8, IL-6, TNF and IL-1β was higher in uninfected BECs from COPD patients compared to healthy subjects but there was no difference in pro-inflammatory response to RV between groups. Conclusions IFN responses to RV was impaired in alveolar macrophages from COPD patients and further reduced in patients with frequent exacerbations.