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Human Rhinovirus Impairs the Innate Immune Response to Bacteria in Alveolar Macrophages in COPD

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Title: Human Rhinovirus Impairs the Innate Immune Response to Bacteria in Alveolar Macrophages in COPD
Authors: Finney, LJ
Belchamber, KBR
Fenwick, PS
Kemp, SV
Edwards, MR
Mallia, P
Donaldson, G
Johnston, SL
Donnelly, LE
Wedzicha, JA
Item Type: Journal Article
Abstract: Rationale Human rhinovirus (HRV) is a common cause of 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 controls. Methods Alveolar macrophages were obtained by bronchoscopy and MDM by adherence. Macrophages were exposed to HRV 16 (multiplicity of infection 5), polyI:C 30μg/ml, interferon (IFN)-β 10μg/ml, IFN-γ 10μg/ml or medium control for 24 hours. Phagocytosis of fluorescently-labelled Haemophilus influenzae or Streptococcus pneumoniae was assessed by fluorimetry. CXCL8, TNF and IL-10 release was measured by ELISA. Main Results HRV significantly impaired phagocytosis of H. influenzae by 23% in MDM (n=37) and 18% in alveolar macrophages (n=20) in COPD. HRV also significantly reduced phagocytosis of S. pneumoniae by 33% in COPD MDM. There was no effect in healthy controls. Phagocytosis of H. influenzae was impaired by polyI:C but not IFN-β or IFN-γ. HRV significantly reduced cytokine responses to H. influenzae. The IL-10 response to H. influenzae was significantly impaired by polyI:C, IFN-β and IFN-γ. 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.
Issue Date: 18-Dec-2018
Date of Acceptance: 14-Dec-2018
URI: http://hdl.handle.net/10044/1/66810
DOI: https://dx.doi.org/10.1164/rccm.201806-1095OC
ISSN: 1073-449X
Publisher: American Thoracic Society
Journal / Book Title: American Journal of Respiratory and Critical Care Medicine
Copyright Statement: © 2018 by the American Thoracic Society
Sponsor/Funder: Royal Brompton & Harefield NHS Foundation Trust
Janssen Research & Development Llc
Funder's Grant Number: RCF funding from LNW CRN
n/a
Keywords: Bacteria
COPD
Macrophages
Phagocytosis
Rhinovirus
11 Medical And Health Sciences
Respiratory System
Publication Status: Published online
Conference Place: United States
Embargo Date: 2019-12-18
Online Publication Date: 2018-12-18
Appears in Collections:National Heart and Lung Institute
Airway Disease
Faculty of Medicine



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