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Respirology. 2016 Jan;21(1):172-9. doi: 10.1111/resp.12657. Epub 2015 Oct 18.

Differential neutrophil activation in viral infections: Enhanced TLR-7/8-mediated CXCL8 release in asthma.

Author information

1
Woolcock Institute of Medical Research, The University of Sydney, Sydney, New South Wales, Australia.
2
Discipline of Pharmacology, School of Medical Sciences, Faculty of Medicine, The University of Sydney, Sydney, New South Wales, Australia.
3
Genome Integrity Group, The Children's Medical Research Institute, Sydney, New South Wales, Australia.
4
School of Biomedical Science, Faculty of Health, Queensland University of Technology, Brisbane, Queensland, Australia.
5
WHO Collaborating Centre for Reference and Research on Influenza, Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
6
Department of Pediatrics I, University of Tübingen, Tübingen, Germany.
7
Priority Research Centre for Asthma and Respiratory Disease, The University of Newcastle, Newcastle, New South Wales, Australia.
8
School of Medical and Molecular Biosciences, University of Technology Sydney, Sydney, New South Wales, Australia.

Abstract

BACKGROUND AND OBJECTIVE:

Respiratory viral infections are a major cause of asthma exacerbations. Neutrophils accumulate in the airways and the mechanisms that link neutrophilic inflammation, viral infections and exacerbations are unclear. This study aims to investigate anti-viral responses in neutrophils from patients with and without asthma and to investigate if neutrophils can be directly activated by respiratory viruses.

METHODS:

Neutrophils from peripheral blood from asthmatic and non-asthmatic individuals were isolated and stimulated with lipopolysaccharide (LPS) (1 μg/mL), f-met-leu-phe (fMLP) (100 nM), imiquimod (3 μg/mL), R848 (1.5 μg/mL), poly I:C (10 μg/mL), RV16 (multiplicity of infection (MOI)1), respiratory syncytial virus (RSV) (MOI1) or influenza virus (MOI1). Cell-free supernatants were collected after 1 h of neutrophil elastase (NE) and matrix metalloproteinase (MMP)-9 release, or after 24 h for CXCL8 release.

RESULTS:

LPS, fMLP, imiquimod and R848 stimulated the release of CXCL8, NE and MMP-9 whereas poly I:C selectively induced CXCL8 release only. R848-induced CXCL8 release was enhanced in neutrophils from asthmatics compared with non-asthmatic cells (P < 0.01). RSV triggered the release of CXCL8 and NE from neutrophils, whereas RV16 or influenza had no effect.

CONCLUSION:

Neutrophils release CXCL8, NE and MMP-9 in response to viral surrogates with R848-induced CXCL8 release being specifically enhanced in asthmatic neutrophils. Toll-like receptor (TLR7/8) dysregulation may play a role in neutrophilic inflammation in viral-induced exacerbations.

KEYWORDS:

asthma; innate immune responses; neutrophils; respiratory viruses; rhinovirus

PMID:
26477783
PMCID:
PMC5324549
DOI:
10.1111/resp.12657
[Indexed for MEDLINE]
Free PMC Article

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