Neutrophil extracellular traps promote immunopathogenesis of virus-induced COPD exacerbations.

Autor: Katsoulis O; Department of Infectious Disease, Centre for Bacterial Resistance Biology, Imperial College London, London, UK., Toussaint M; National Heart and Lung Institute, Imperial College London, London, UK., Jackson MM; Department of Infectious Disease, Centre for Bacterial Resistance Biology, Imperial College London, London, UK., Mallia P; National Heart and Lung Institute, Imperial College London, London, UK., Footitt J; National Heart and Lung Institute, Imperial College London, London, UK., Mincham KT; National Heart and Lung Institute, Imperial College London, London, UK., Meyer GFM; National Heart and Lung Institute, Imperial College London, London, UK., Kebadze T; National Heart and Lung Institute, Imperial College London, London, UK., Gilmour A; Division of Molecular and Clinical Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK., Long M; Division of Molecular and Clinical Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK., Aswani AD; Department of Intensive Care Medicine, Guy's and St Thomas' NHS Foundation Trust, London, SE1 7EH, UK., Snelgrove RJ; National Heart and Lung Institute, Imperial College London, London, UK., Johnston SL; National Heart and Lung Institute, Imperial College London, London, UK., Chalmers JD; Division of Molecular and Clinical Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK., Singanayagam A; Department of Infectious Disease, Centre for Bacterial Resistance Biology, Imperial College London, London, UK. a.singanayagam@imperial.ac.uk.; National Heart and Lung Institute, Imperial College London, London, UK. a.singanayagam@imperial.ac.uk.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Jul 09; Vol. 15 (1), pp. 5766. Date of Electronic Publication: 2024 Jul 09.
DOI: 10.1038/s41467-024-50197-0
Abstrakt: Respiratory viruses are a major trigger of exacerbations in chronic obstructive pulmonary disease (COPD). Airway neutrophilia is a hallmark feature of stable and exacerbated COPD but roles played by neutrophil extracellular traps (NETS) in driving disease pathogenesis are unclear. Here, using human studies of experimentally-induced and naturally-occurring exacerbations we identify that rhinovirus infection induces airway NET formation which is amplified in COPD and correlates with magnitude of inflammation and clinical exacerbation severity. We show that inhibiting NETosis protects mice from immunopathology in a model of virus-exacerbated COPD. NETs drive inflammation during exacerbations through release of double stranded DNA (dsDNA) and administration of DNAse in mice has similar protective effects. Thus, NETosis, through release of dsDNA, has a functional role in the pathogenesis of COPD exacerbations. These studies open up the potential for therapeutic targeting of NETs or dsDNA as a strategy for treating virus-exacerbated COPD.
(© 2024. The Author(s).)
Databáze: MEDLINE
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