Imperial College London
Alternate

ProfessorSebastianJohnston

Faculty of Medicine, National Heart & Lung Institute

Asthma UK Clinical Chair
 
 
 
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Contact

 

+44 (0)7931 376 544s.johnston

 
 
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Assistant

 

Mr Christophe Tytgat +44 (0)20 7594 3849

 
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Location

 

343Norfolk PlaceSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Finney:2019:10.1164/rccm.201806-1095OC,
author = {Finney, LJ and Belchamber, KBR and Fenwick, PS and Kemp, SV and Edwards, MR and Mallia, P and Donaldson, G and Johnston, SL and Donnelly, LE and Wedzicha, JA},
doi = {10.1164/rccm.201806-1095OC},
journal = {American Journal of Respiratory and Critical Care Medicine},
pages = {1496--1507},
title = {Human rhinovirus impairs the innate immune response to bacteria in alveolar macrophages in chronic obstructive pulmonary disease},
url = {http://dx.doi.org/10.1164/rccm.201806-1095OC},
volume = {199},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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.
AU  - Finney,LJ
AU  - Belchamber,KBR
AU  - Fenwick,PS
AU  - Kemp,SV
AU  - Edwards,MR
AU  - Mallia,P
AU  - Donaldson,G
AU  - Johnston,SL
AU  - Donnelly,LE
AU  - Wedzicha,JA
DO  - 10.1164/rccm.201806-1095OC
EP  - 1507
PY  - 2019///
SN  - 1073-449X
SP  - 1496
TI  - Human rhinovirus impairs the innate immune response to bacteria in alveolar macrophages in chronic obstructive pulmonary disease
T2  - American Journal of Respiratory and Critical Care Medicine
UR  - http://dx.doi.org/10.1164/rccm.201806-1095OC
UR  - https://www.ncbi.nlm.nih.gov/pubmed/30562053
UR  - https://www.atsjournals.org/doi/10.1164/rccm.201806-1095OC
UR  - http://hdl.handle.net/10044/1/66810
VL  - 199
ER  -
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