Human Rhinovirus 16 Infection of Human Macrophages Impairs Their Clearance Ability by Perturbing Phagosome Maturation

Introduction & Hypothesis: Chronic obstructive pulmonary disease (COPD) is characterized by increased numbers of Alveolar macrophages (AMs) with diminished phagocytic function. This could drive exacerbations where human rhinovirus (HRV) is frequently isolated. We hypothesised that HRV infection of macrophages was driving this phagocytic impairment. Methods: AMs or monocyte derived macrophages (MDMs) were challenged with HRV16 and the endocytic machinery analysed by microscopy. We also analysed the recruitment of endocytic markers around phagosomes in infected macrophages following HRV16 infection and a second trigger. Finally, we quantified the expression and localisation of these markers in infected macrophages by western blotting and flow cytometry. Results: We found endocytic markers were mislocalised with altered expression profiles in infected macrophages and not properly recruited around phagosomes, impairing phagosome maturation and clearance. Reactive oxygen species (ROS) and hydrolase production was impaired in infected macrophages also perturbing clearance. Lastly, microtubule dynamics were affected in infected macrophages impairing clearance further. We are currently using in depth cell biology to explore host proteins we believe HRV16 affects driving these defects. Conclusion: Our results demonstrate HRV16 impairs intracellular clearance in macrophages by perturbing the endocytic machinery and affecting microtubule dynamics. They could explain why COPD patients show virus induced exacerbations and secondary bacterial infections. Further analysis of how HRV16 hijacks these pathways offers the potential to design novel therapeutics to treat COPD exacerbations.