Human rhinovirus impairs the innate immune response to bacteria in alveolar macrophages in chronic obstructive pulmonary disease

Research output: Contribution to journalArticlepeer-review

Authors

  • Lydia J Finney
  • Peter S Fenwick
  • Samuel V Kemp
  • Michael R Edwards
  • Patrick Mallia
  • Gavin Donaldson
  • Sebastian L Johnston
  • Louise E Donnelly
  • Jadwiga A Wedzicha

Colleges, School and Institutes

External organisations

  • Imperial College London
  • Royal Brompton Hospital

Abstract

Rationale

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. 

Objectives

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. 

Methods

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 Haemophilus influenzae or Streptococcus pneumoniae was assessed by fluorimetry. CXCL8 (IL-8), IL-6, TNF-α (tumor necrosis factor-α), and IL-10 release was measured by ELISA. 

Measurements and Main Results

HRV significantly impaired phagocytosis of H. influenzae by 23% in MDM (n = 37; P = 0.004) and 18% in alveolar macrophages (n = 20; P < 0.0001) in COPD. HRV also significantly reduced phagocytosis of S. pneumoniae by 33% in COPD MDM (n = 20; P = 0.0192). There was no effect in healthy control subjects. Phagocytosis of H. influenzae was also impaired by poly I:C but not IFN-β or IFN-γ in COPD MDM. HRV significantly reduced cytokine responses to H. influenzae. The IL-10 response to H. influenzae was significantly impaired by poly I:C, IFN-β, and IFN-γ in COPD cells. 

Conclusions

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.

Details

Original languageEnglish
Pages (from-to)1496-1507
Number of pages12
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume199
Issue number12
Early online date18 Dec 2018
Publication statusPublished - 15 Jun 2019

Keywords

  • COPD, macrophages, rhinovirus, phagocytosis, bacteria