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

Francesca S.M. Tang*, David Van Ly, Kirsten Spann, Patrick C. Reading, Janette K. Burgess, Dominik Hartl, Katherine J. Baines, Brian G. Oliver

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

29 Citations (Scopus)
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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. We aimed to investigate and compare neutrophil responses to bacterial compounds and viral mimetics as well as compare responses between people with and without asthma. We also investigated neutrophil responses to live respiratory viruses. Here we provide a novel comprehensive comparison showing differential and specific activation in innate immune cells. See Editorial, page 10
Original languageEnglish
Pages (from-to)172-179
Number of pages8
JournalRespirology
Volume21
Issue number1
DOIs
Publication statusPublished - Jan-2016

Keywords

  • asthma
  • innate immune responses
  • neutrophils
  • respiratory viruses
  • rhinovirus
  • beta 2 adrenergic receptor stimulating agent
  • corticosteroid
  • formylmethionylleucylphenylalanine
  • gelatinase B
  • imiquimod
  • interleukin 8
  • leukocyte elastase
  • lipopolysaccharide
  • polyinosinic polycytidylic acid
  • resiquimod
  • short acting drug
  • toll like receptor 7
  • toll like receptor 8
  • adult
  • article
  • cell isolation
  • clinical article
  • controlled study
  • cytokine release
  • degranulation
  • disease exacerbation
  • enzyme activity
  • enzyme linked immunosorbent assay
  • enzyme release
  • female
  • forced expiratory volume
  • human
  • human cell
  • Human respiratory syncytial virus
  • Human rhinovirus
  • Influenza virus
  • innate immunity
  • leukocyte activation
  • male
  • neutrophil
  • priority journal
  • protein function
  • respiratory virus
  • reverse transcription polymerase chain reaction
  • supernatant
  • viral respiratory tract infection
  • virus replication

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