title: Differential neutrophil activation in viral infections: Enhanced TLR-7/8-mediated CXCL8 release in asthma.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Woolcock Institute of Medical Research, The University of Sydney, Sydney, New South Wales, Australia.|Discipline of Pharmacology, School of Medical Sciences, Faculty of Medicine, The University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Francesca S M
authors.initials: FS
authors.lastname: Tang
authors.affiliation: Woolcock Institute of Medical Research, The University of Sydney, Sydney, New South Wales, Australia.|Genome Integrity Group, The Children's Medical Research Institute, Sydney, New South Wales, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Van Ly
authors.affiliation: School of Biomedical Science, Faculty of Health, Queensland University of Technology, Brisbane, Queensland, Australia.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Spann
authors.affiliation: WHO Collaborating Centre for Reference and Research on Influenza, Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
authors.forename: Patrick C
authors.initials: PC
authors.lastname: Reading
authors.affiliation: Woolcock Institute of Medical Research, The University of Sydney, Sydney, New South Wales, Australia.|Discipline of Pharmacology, School of Medical Sciences, Faculty of Medicine, The University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Janette K
authors.initials: JK
authors.lastname: Burgess
authors.affiliation: Department of Pediatrics I, University of Tübingen, Tübingen, Germany.
authors.forename: Dominik
authors.initials: D
authors.lastname: Hartl
authors.affiliation: Priority Research Centre for Asthma and Respiratory Disease, The University of Newcastle, Newcastle, New South Wales, Australia.
authors.forename: Katherine J
authors.initials: KJ
authors.lastname: Baines
authors.affiliation: Woolcock Institute of Medical Research, The University of Sydney, Sydney, New South Wales, Australia.|School of Medical and Molecular Biosciences, University of Technology Sydney, Sydney, New South Wales, Australia.
authors.forename: Brian G
authors.initials: BG
authors.lastname: Oliver
mesh_terms: D000328:Adult; D001249:Asthma / Q000276:immunology / Q000503:physiopathology / Q000821:virology; D005260:Female; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000503:physiopathology; D016209:Interleukin-8 / Q000378:metabolism; D019272:Leukocyte Elastase / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000378:metabolism*; D018375:Neutrophil Activation / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology*; D009975:Orthomyxoviridae / Q000502:physiology; D012136:Respiratory Syncytial Viruses / Q000502:physiology; D000067251:Symptom Flare Up; D051193:Toll-Like Receptors / Q000276:immunology; D014777:Virus Diseases / Q000150:complications / Q000276:immunology
chemical_list: C508606:CXCL8 protein, human; D016209:Interleukin-8; D008070:Lipopolysaccharides; D051193:Toll-Like Receptors; D009240:N-Formylmethionine Leucyl-Phenylalanine; D019272:Leukocyte Elastase; D020780:Matrix Metalloproteinase 9
keywords: asthma; innate immune responses; neutrophils; respiratory viruses; rhinovirus