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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Asthma* / immunology
  • Asthma* / physiopathology
  • Asthma* / virology
  • Female
  • Humans
  • Inflammation / immunology
  • Inflammation / physiopathology
  • Interleukin-8 / metabolism
  • Leukocyte Elastase / metabolism
  • Lipopolysaccharides / metabolism*
  • Male
  • Matrix Metalloproteinase 9 / metabolism
  • N-Formylmethionine Leucyl-Phenylalanine / metabolism*
  • Neutrophil Activation / immunology*
  • Neutrophils / immunology*
  • Orthomyxoviridae / physiology
  • Respiratory Syncytial Viruses / physiology
  • Symptom Flare Up
  • Toll-Like Receptors / immunology
  • Virus Diseases* / complications
  • Virus Diseases* / immunology


  • CXCL8 protein, human
  • Interleukin-8
  • Lipopolysaccharides
  • Toll-Like Receptors
  • N-Formylmethionine Leucyl-Phenylalanine
  • Leukocyte Elastase
  • Matrix Metalloproteinase 9