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

被引：266

作者：

Toussaint, Marie ^{[1
,2
,3
]}

Jackson, David J. ^{[1
,2
,3
,4
,5
]}

Swieboda, Dawid ^{[1
,2
,3
]}

Guedan, Anabel ^{[1
,2
,3
]}

Tsourouktsoglou, Theodora-Dorita

Ching, Yee Man ^{[1
,2
,3
]}

Radermecker, Coraline ^{[7
,8
]}

Makrinioti, Heidi ^{[1
,2
,3
]}

Aniscenko, Julia ^{[1
,2
,3
]}

Edwards, Michael R. ^{[1
,2
,3
]}

Solari, Roberto ^{[1
,2
,3
]}

Farnir, Frederic ^{[8
,9
]}

Papayannopoulos, Venizelos ^{[6
]}

Bureau, Fabrice ^{[7
,8
,10
]}

Marichal, Thomas ^{[7
,8
]}

Johnston, Sebastian L. ^{[1
,2
,3
,4
]}

机构：

[1] Imperial Coll London, Natl Heart & Lung Inst, Airway Dis Infect Sect, London, England

[2] MRC, London, England

[3] Asthma UK Ctr Allerg Mech Asthma, London, England

[4] Imperial Coll Healthcare NHS Trust, London, England

[5] Guys & St Thomas NHS Trust, London, England

[6] Francis Crick Inst, London, England

[7] Univ Liege, Grp Interdisciplinaire Genoprote Appl, Lab Cellular & Mol Immunol, Liege, Belgium

[8] Univ Liege, Fac Vet Med, Liege, Belgium

[9] Univ Liege, Fundamental & Appl Res Anim & Hlth, Liege, Belgium

[10] Walloon Excellence Life Sci & Biotechnol, WELBIO, Wallonia, Belgium

来源：

NATURE MEDICINE | 2017年 / 23卷 / 06期

基金：

英国医学研究理事会; 欧洲研究理事会;

关键词：

NEUTROPHIL EXTRACELLULAR TRAPS; PLASMACYTOID DENDRITIC CELLS; MOUSE MODEL; ELASTASE; INFLAMMATION; INFECTION; HYPERRESPONSIVENESS; CHALLENGE; CYTOKINES; SEVERITY;

D O I：

10.1038/nm.4332

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：681 / +

页数：14

共 57 条

[1] Mouse models of rhinovirus-induced disease and exacerbation of allergic airway inflammation [J].