1. Neutrophil extracellular traps promote immunopathogenesis of virus-induced COPD exacerbations.
- Author
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Katsoulis O, Toussaint M, Jackson MM, Mallia P, Footitt J, Mincham KT, Meyer GFM, Kebadze T, Gilmour A, Long M, Aswani AD, Snelgrove RJ, Johnston SL, Chalmers JD, and Singanayagam A
- Subjects
- Animals, Humans, Mice, Male, Female, Picornaviridae Infections immunology, Picornaviridae Infections virology, Picornaviridae Infections complications, Mice, Inbred C57BL, DNA immunology, Disease Models, Animal, Middle Aged, Inflammation immunology, Inflammation virology, Aged, Extracellular Traps immunology, Pulmonary Disease, Chronic Obstructive immunology, Pulmonary Disease, Chronic Obstructive virology, Pulmonary Disease, Chronic Obstructive pathology, Rhinovirus immunology, Neutrophils immunology
- Abstract
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).)
- Published
- 2024
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