Differential neutrophil activation in viral infections: Enhanced TLR-7/8-mediated CXCL8 release in asthma
Web of Science
AuthorTang, FSM; Van Ly, D; Spann, K; Reading, PC; Burgess, JK; Hartl, D; Baines, KJ; Oliver, BG
University of Melbourne Author/sReading, Patrick
AffiliationMicrobiology and Immunology
Document TypeJournal Article
CitationsTang, F. S. M., Van Ly, D., Spann, K., Reading, P. C., Burgess, J. K., Hartl, D., Baines, K. J. & Oliver, B. G. (2016). Differential neutrophil activation in viral infections: Enhanced TLR-7/8-mediated CXCL8 release in asthma. RESPIROLOGY, 21 (1), pp.172-179. https://doi.org/10.1111/resp.12657.
Access StatusOpen Access
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.
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