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

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Title: Host DNA released by NETosis promotes rhinovirus-induced type-2 allergic asthma exacerbation
Authors: Toussaint, M
Jackson, DJ
Swieboda, D
Guedan, A
Tsourouktsoglou, T-D
Ching, YM
Radermecker, C
Makrinioti, H
Aniscenko, J
Edwards, MR
Solari, R
Farnir, F
Papayannopoulos, V
Bureau, F
Marichal, T
Johnston, SL
Item Type: Journal Article
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.
Issue Date: 1-May-2017
Date of Acceptance: 4-Apr-2017
URI: http://hdl.handle.net/10044/1/49463
DOI: https://dx.doi.org/10.1038/nm.4332
ISSN: 1078-8956
Publisher: NATURE PUBLISHING GROUP
Start Page: 681
End Page: 691
Journal / Book Title: NATURE MEDICINE
Volume: 23
Issue: 6
Copyright Statement: © 2017 Nature America, Inc., part of Springer Nature. All rights reserved. The final publication is available at https://dx.doi.org/10.1038/nm.4332
Sponsor/Funder: Commission of the European Communities
Commission of the European Communities
Asthma UK
Asthma UK
National Institute for Health Research
Asthma UK
Funder's Grant Number: 233015
260895
CH11SJ
CH11SJ
NF-SI-0514-10092
Asthma UK Centre
Keywords: Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
Cell Biology
Medicine, Research & Experimental
Research & Experimental Medicine
NEUTROPHIL EXTRACELLULAR TRAPS
PLASMACYTOID DENDRITIC CELLS
ANTIMICROBIAL PEPTIDE
AIRWAY INFLAMMATION
VIRUS-INFECTION
MOUSE MODEL
IN-VIVO
ELASTASE
HYPERRESPONSIVENESS
DIFFERENTIATION
11 Medical And Health Sciences
Immunology
Publication Status: Published
Appears in Collections:National Heart and Lung Institute
Faculty of Medicine



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