127
IRUS TotalDownloads
Host DNA released by NETosis promotes rhinovirus-induced type-2 allergic asthma exacerbation
File | Description | Size | Format | |
---|---|---|---|---|
![]() | Accepted version | 196.2 kB | Microsoft Word | View/Open |
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 |