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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-Jun-2017
Date of Acceptance: 4-Apr-2017
URI: http://hdl.handle.net/10044/1/49463
DOI: 10.1038/nm.4332
ISSN: 1078-8956
Publisher: Nature Research
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: Asthma UK
Asthma UK
Asthma UK
Commission of the European Communities
National Institute for Health Research
Commission of the European Communities
Medical Research Council (MRC)
Medical Research Council (MRC)
Medical Research Council (MRC)
Medical Research Council (MRC)
Medical Research Council (MRC)
Medical Research Council (MRC)
Medical Research Council (MRC)
Innovate UK
Asthma UK
Asthma UK
Asthma UK
Funder's Grant Number: Asthma UK Centre
CH11SJ
CH11SJ
260895
NF-SI-0514-10092
233015
G0601236
G0600879
G1000758
G1100168
G1100238
G1000758
MR/L012693/1
MR/M025330/1
06/050
08/048
08/048
Keywords: Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
Cell Biology
Medicine, Research & Experimental
Research & Experimental Medicine
NEUTROPHIL EXTRACELLULAR TRAPS
PLASMACYTOID DENDRITIC CELLS
MOUSE MODEL
ELASTASE
INFLAMMATION
INFECTION
HYPERRESPONSIVENESS
CHALLENGE
CYTOKINES
SEVERITY
Adult
Animals
Asthma
Case-Control Studies
Cytokines
DNA
Dermatophagoides farinae
Disease Models, Animal
Extracellular Traps
Female
Humans
Interferon-gamma
Interleukin-13
Interleukin-4
Interleukin-5
Male
Mice
Middle Aged
Picornaviridae Infections
Respiratory Hypersensitivity
Respiratory Tract Infections
Rhinovirus
Th2 Cells
Young Adult
Th2 Cells
Animals
Humans
Mice
Dermatophagoides farinae
Rhinovirus
Respiratory Tract Infections
Picornaviridae Infections
Asthma
Respiratory Hypersensitivity
Disease Models, Animal
DNA
Interleukin-4
Interleukin-5
Interleukin-13
Cytokines
Case-Control Studies
Adult
Middle Aged
Female
Male
Interferon-gamma
Young Adult
Extracellular Traps
Immunology
11 Medical and Health Sciences
Publication Status: Published
Open Access location: http://hdl.handle.net/10044/1/49463
Online Publication Date: 2017-05-01
Appears in Collections:National Heart and Lung Institute
Faculty of Medicine