Neutrophil extracellular traps promote immunopathogenesis of virus-induced COPD exacerbations

Orestis Katsoulis, Marie Toussaint, Millie M. Jackson, Patrick Mallia, Joseph Footitt, Kyle T. Mincham, Garance F.M. Meyer, Tata Kebadze, Amy Gilmour, Merete Long, Andrew D. Aswani, Robert J. Snelgrove, Sebastian L. Johnston, James D. Chalmers, Aran Singanayagam (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)
39 Downloads (Pure)

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.

Original languageEnglish
Article number5766
Number of pages14
JournalNature Communications
Volume15
DOIs
Publication statusPublished - 9 Jul 2024

ASJC Scopus subject areas

  • General Chemistry
  • General Biochemistry,Genetics and Molecular Biology
  • General Physics and Astronomy

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