Host DNA released by NETosis promotes rhinovirus-induced type-2 allergic asthma exacerbation
Marie Toussaint,David A. Jackson,Dawid Swieboda,Anabel Guedán,Theodora-Dorita Tsourouktsoglou,Yee Man Ching,Coraline Radermecker,Heidi Makrinioti,Julia Aniscenko,Michael R. Edwards,Roberto Solari,Frédéric Farnir,Venizelos Papayannopoulos,Fabrice Bureau,Thomas Marichal,Sebastian L. Johnston +15 more
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TLDR
In a mouse model of allergic airway hypersensitivity, it is shown that rhinovirus infection triggers dsDNA release associated with the formation of neutrophil extracellular traps (NETs), known as NETosis, which contribute to the pathogenesis and may represent potential therapeutic targets of rhinOVirus-induced asthma exacerbations.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.read more
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Immunoglobulin E-Dependent Activation of Immune Cells in Rhinovirus-Induced Asthma Exacerbation
TL;DR: Possible IgE-dependent roles of mast cells and dendritic cells in asthma exacerbations are discussed, and mechanistic details of omalizumab's effects on RV-induced asthma exacerbation have not been well-defined for years due to the lack of appropriate animal models.
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Neutrophil Extracellular Traps Are Found in Bronchoalveolar Lavage Fluids of Horses With Severe Asthma and Correlate With Asthma Severity
Pierre Janssen,Irène Tosi,Alexandre Hego,Pauline Maréchal,Thomas Marichal,Coraline Radermecker +5 more
TL;DR: This study uniquely identifies the presence of neutrophil extracellular traps in BALF of severe asthmatic horses using three distinct methods and supports the idea that moderate and severe equine asthma do not rely on strictly similar pathophysiological mechanisms.
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Neutrophil phenotypes in bronchial airways differentiate single from dual responding allergic asthmatics
N. van der Burg,Henning Stenberg,Sandra Ekstedt,Zuzana Diamant,Daisy Bornesund,Jaro Ankerst,Susanna Kumlien Georén,Lars-Olaf Cardell,Leif Bjermer,Jonas S. Erjefält,Ellen Tufvesson +10 more
TL;DR: DR have a more active airway neutrophils phenotype at baseline and a distinct neutrophil response to allergen challenge that may contribute to the development of an LAR, and neutrophIL activity should be considered during targeted diagnosis and bio-therapeutic development for DR.
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Allergen-induced DNA release by the airway epithelium amplifies type 2 immunity.
Yotesawee Srisomboon,Koji Iijima,Mathia Colwell,Peter J. Maniak,Marissa Macchietto,Christopher Faulk,Hirohito Kita,Scott M. O'Grady +7 more
TL;DR: In this article , the authors investigated the mechanisms underlying allergen-evoked DNA mobilization and release from the airway epithelium and determined the role of eDNA in type 2 immunity.
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The Pathology of Asthma: What Is Obstructing Our View?
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TL;DR: The evidence is examined that mucus plugs contribute to a substantial portion of disease, not only by physically obstructing the airways but also by perpetuating inflammation.
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Neutrophil extracellular traps kill bacteria
Volker Brinkmann,Ulrike Reichard,Christian Goosmann,Beatrix Fauler,Yvonne Uhlemann,David S. Weiss,Yvette Weinrauch,Yvette Weinrauch,Arturo Zychlinsky +8 more
TL;DR: It is described that, upon activation, neutrophils release granule proteins and chromatin that together form extracellular fibers that bind Gram-positive and -negative bacteria, which degrade virulence factors and kill bacteria.
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Extracellular DNA traps promote thrombosis
Tobias A. Fuchs,Alexander Brill,Daniel Duerschmied,Daphne Schatzberg,Marc Monestier,Daniel D. Myers,Shirley K. Wrobleski,Thomas W. Wakefield,John H. Hartwig,Denisa D. Wagner +9 more
TL;DR: It is reported that NETs provide a heretofore unrecognized scaffold and stimulus for thrombus formation and may further explain the epidemiological association of infection with thrombosis.
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Roberto Lande,Josh Gregorio,Valeria Facchinetti,Bithi Chatterjee,Bithi Chatterjee,Yi Hong Wang,Bernhard Homey,Wei Cao,Yui-Hsi Wang,Bing Su,Frank O. Nestle,Tomasz Zal,Ira Mellman,Ira Mellman,Jens-Michael Schröder,Yong-Jun Liu,Michel Gilliet +16 more
TL;DR: The data uncover a fundamental role of an endogenous antimicrobial peptide in breaking innate tolerance to self-DNA and suggest that this pathway may drive autoimmunity in psoriasis.