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

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

doi:10.1164/rccm.201806-1095OC

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

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

Inflammation and Ageing

Research output: Contribution to journal › Article › peer-review

18 Citations (Scopus)

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.

Original language	English
Pages (from-to)	1496-1507
Number of pages	12
Journal	American Journal of Respiratory and Critical Care Medicine
Volume	199
Issue number	12
Early online date	18 Dec 2018
DOIs	https://doi.org/10.1164/rccm.201806-1095OC
Publication status	Published - 15 Jun 2019

Keywords

COPD
bacteria
macrophages
phagocytosis
rhinovirus

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1164/rccm.201806-1095OCLicence: None: All rights reserved

Cite this

Finney, L. J., Belchamber, K. B. R., Fenwick, P. S., Kemp, S. V., Edwards, M. R., Mallia, P., Donaldson, G., Johnston, S. L., Donnelly, L. E., & Wedzicha, J. A. (2019). Human rhinovirus impairs the innate immune response to bacteria in alveolar macrophages in chronic obstructive pulmonary disease. American Journal of Respiratory and Critical Care Medicine, 199(12), 1496-1507. Advance online publication. https://doi.org/10.1164/rccm.201806-1095OC

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

abstract = "RationaleHuman 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. ObjectivesTo 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. MethodsAlveolar 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 ResultsHRV 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. ConclusionsHRV 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.",

keywords = "COPD, bacteria, macrophages, phagocytosis, rhinovirus",

author = "Finney, {Lydia J} and Belchamber, {Kylie B R} and Fenwick, {Peter S} and Kemp, {Samuel V} and Edwards, {Michael R} and Patrick Mallia and Gavin Donaldson and Johnston, {Sebastian L} and Donnelly, {Louise E} and Wedzicha, {Jadwiga A}",

year = "2019",

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doi = "10.1164/rccm.201806-1095OC",

language = "English",

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pages = "1496--1507",

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Finney, LJ, Belchamber, KBR, Fenwick, PS, Kemp, SV, Edwards, MR, Mallia, P, Donaldson, G, Johnston, SL, Donnelly, LE & Wedzicha, JA 2019, 'Human rhinovirus impairs the innate immune response to bacteria in alveolar macrophages in chronic obstructive pulmonary disease', American Journal of Respiratory and Critical Care Medicine, vol. 199, no. 12, pp. 1496-1507. https://doi.org/10.1164/rccm.201806-1095OC

Human rhinovirus impairs the innate immune response to bacteria in alveolar macrophages in chronic obstructive pulmonary disease. / Finney, Lydia J; Belchamber, Kylie B R; Fenwick, Peter S et al.
In: American Journal of Respiratory and Critical Care Medicine, Vol. 199, No. 12, 15.06.2019, p. 1496-1507.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Human rhinovirus impairs the innate immune response to bacteria in alveolar macrophages in chronic obstructive pulmonary disease

AU - Finney, Lydia J

AU - Belchamber, Kylie B R

AU - Fenwick, Peter S

AU - Kemp, Samuel V

AU - Edwards, Michael R

AU - Mallia, Patrick

AU - Donaldson, Gavin

AU - Johnston, Sebastian L

AU - Donnelly, Louise E

AU - Wedzicha, Jadwiga A

PY - 2019/6/15

Y1 - 2019/6/15

N2 - RationaleHuman 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. ObjectivesTo 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. MethodsAlveolar 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 ResultsHRV 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. ConclusionsHRV 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.

AB - RationaleHuman 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. ObjectivesTo 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. MethodsAlveolar 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 ResultsHRV 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. ConclusionsHRV 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.

KW - COPD

KW - bacteria

KW - macrophages

KW - phagocytosis

KW - rhinovirus

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U2 - 10.1164/rccm.201806-1095OC

DO - 10.1164/rccm.201806-1095OC

M3 - Article

C2 - 30562053

SN - 1073-449X

VL - 199

SP - 1496

EP - 1507

JO - American Journal of Respiratory and Critical Care Medicine

JF - American Journal of Respiratory and Critical Care Medicine

IS - 12

ER -

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

Abstract

Keywords

UN SDGs

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