Abstract
Background: Alveolar macrophages (AMs) play key roles in the pathogenesis of chronic obstructive pulmonary disease (COPD). The aim of this study was to characterise the mechanisms of defective phagocytosis in AMs from COPD patients. We hypothesised that respiratory viruses could impair the ability of AMs to phagocytose lung bacteria. Materials and methods: AMs were isolated from bronchoalveolar lavage (BAL) and phenotyped using flow cytometry. AMs were pre-challenged with major or minor group rhinoviruses (RVs) and then phagocytosis of Moraxella catarrhalis or non-typeable Haemophilus influenzae (NTHi) examined. We repeated experiments using monocyte-derived macrophages (MDMs). Results: AMs consisted of separate populations. AMs from COPD patients had reduced cell surface marker expression, were immature and defective in phagocytosis and bacterial clearance. AMs pre-infected with major group RVs showed reduced phagocytosis, not seen in AMs pre-infected with a minor group RV. This inhibition was likely viral mediated because it was not observed in AMs treated with UV inactivated virus. Using MDMs we observed the same. We are currently investigating how viral infection or viral products affect the capacities of macrophages to engulf bacteria, generate phagolysosomes and eliminate them, and produce cytokines. Conclusion: Our results suggest AMs from COPD patients are phenotypically different to AMs from healthy patients and defective in phagocytosis. We show major group RVs impair AM and MDM phagocytic functions. These results could explain why COPD patients show exacerbations with bacterial pathogens found in the lung and why they show infections with major group RVs first.
Published Version
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