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Nat Med. 2017 Jun;23(6):681-691. doi: 10.1038/nm.4332. Epub 2017 May 1.

Host DNA released by NETosis promotes rhinovirus-induced type-2 allergic asthma exacerbation.

Author information

1
Airway Disease Infection Section, National Heart and Lung Institute (NHLI), Imperial College London, London, UK.
2
Medical Research Council (MRC) and Asthma UK Centre in Allergic Mechanisms of Asthma, London, UK.
3
Imperial College Healthcare NHS Trust, London, UK.
4
Guy's and St Thomas' NHS Trust, London, UK.
5
The Francis Crick Institute, London, UK.
6
Laboratory of Cellular and Molecular Immunology, Groupe Interdisciplinaire de Génoprotéomique Appliquée (GIGA), University of Liège, Liège, Belgium.
7
Faculty of Veterinary Medicine, University of Liège, Liège, Belgium.
8
Fundamental and Applied Research for Animals &Health, University of Liège, Liège, Belgium.
9
WELBIO, Walloon Excellence in Life Sciences and Biotechnology, Wallonia, Belgium.

Abstract

Respiratory viral infections represent the most common cause of allergic asthma exacerbations. Amplification of the type-2 immune response is strongly implicated in asthma exacerbation, but how virus infection boosts type-2 responses is poorly understood. We report a significant correlation between the release of host double-stranded DNA (dsDNA) following rhinovirus infection and the exacerbation of type-2 allergic inflammation in humans. In a mouse model of allergic airway hypersensitivity, we show that rhinovirus infection triggers dsDNA release associated with the formation of neutrophil extracellular traps (NETs), known as NETosis. We further demonstrate that inhibiting NETosis by blocking neutrophil elastase or by degrading NETs with DNase protects mice from type-2 immunopathology. Furthermore, the injection of mouse genomic DNA alone is sufficient to recapitulate many features of rhinovirus-induced type-2 immune responses and asthma pathology. Thus, NETosis and its associated extracellular dsDNA contribute to the pathogenesis and may represent potential therapeutic targets of rhinovirus-induced asthma exacerbations.

PMID:
28459437
PMCID:
PMC5821220
DOI:
10.1038/nm.4332
[Indexed for MEDLINE]
Free PMC Article

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