NETosis and associated host DNA orchestrate rhinovirus-induced type 2 allergic asthma exacerbation

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Title: NETosis and associated host DNA orchestrate rhinovirus-induced type 2 allergic asthma exacerbation
Authors: Toussaint, M
Swieboda, D
Guedan, A
Jackson, DJ
Tsourouktsoglou, D
Ching, YM
Radermeker, C
Makrinioti, H
Aniescenko, J
Edwards, ME
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 type 2 immunity is strongly implicated in asthma exacerbation, but how virus infection boosts type 2 responses during exacerbation is poorly understood. We report a significant correlation between release of host double stranded DNA (dsDNA) following rhinovirus infection and exacerbation of type 2 allergic inflammation and disease severity in patients. In a mouse model, we show that rhinovirus infection triggers neutrophil extracellular traps (NETs) formation and host dsDNA release. We further demonstrate that inhibiting NETosis by blocking neutrophil elastase or degrading NETs with DNase protects mice from type 2 allergic asthma exacerbations. Furthermore, injection of host dsDNA alone is sufficient to recapitulate many features of rhinovirus-induced type 2 immune responses and asthma pathology. Thus, NETosis and host dsDNA contribute to exacerbation pathogenesis and may represent potential targets for novel treatments of rhinovirus-induced asthma exacerbations.
Date of Acceptance: 30-Jan-2017
URI: http://hdl.handle.net/10044/1/44265
ISSN: 1546-170X
Publisher: Nature Publishing Group
Journal / Book Title: Nature Medicine
Sponsor/Funder: Commission of the European Communities
Medical Research Council (MRC)
Medical Research Council (MRC)
National Institute for Health Research
Funder's Grant Number: 260895
G1000758
G1000758-E01/2
NF-SI-0514-10092
Keywords: Immunology
11 Medical And Health Sciences
Publication Status: Accepted
Appears in Collections:National Heart and Lung Institute
Faculty of Medicine



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