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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The Immune System Throws Its Traps: Cells and Their Extracellular Traps in Disease and Protection.
Fátima Conceição-Silva,Clarissa S M Reis,Paula M. De Luca,Jessica Leite-Silva,Marta A Santiago,Alexandre Morrot,Alexandre Morrot,Fernanda Nazaré Morgado +7 more
TL;DR: The first formal description of the microbicidal activity of extracellular traps (ETs) containing DNA occurred in neutrophils in 2004 and since then, ETs have been identified in different populations of cells involved in both innate and adaptive immune responses as mentioned in this paper.
Journal ArticleDOI
Early recruited neutrophils promote asthmatic inflammation exacerbation by release of neutrophil elastase.
Qingyu Weng,Chen Zhu,Kua Zheng,Yinfang Wu,Ling-Ling Dong,Yanping Wu,Miao Li,Jiaxin Shen,Songmin Ying,Huahao Shen,Zhihua Chen,Wen Li +11 more
TL;DR: The data collectively indicate that neutrophils could contribute to asthmatic inflammation by releasing NE, a component of azurophilic granules and a serine protease with potent functions during inflammation that could capture allergens and release NE to promote neutrophil aggregation at first.
Journal ArticleDOI
Plasma neutrophil extracellular trap level is modified by disease severity and inhaled corticosteroids in chronic inflammatory lung diseases
Zsofia Gal,András Gézsi,András Gézsi,Éva Pállinger,Tamás Visnovitz,Adrienne Nagy,András Kiss,Monika Sultész,Zsuzsanna Csoma,Lilla Tamási,Gabriella Gálffy,Csaba Szalai,Csaba Szalai +12 more
TL;DR: If further studies confirm the NET-lowering effect of ICS in the circulation, it can be utilized in diseases where NETosis contributes to the pathogenesis.
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The Outcome of Neutrophil-T Cell Contact Differs Depending on Activation Status of Both Cell Types.
TL;DR: In this article, the authors established a culture protocol to examine how activated and naive T cells differentially respond to neutrophils, and whether degranulating or resting neutrophil induce different outcomes.
Journal ArticleDOI
Toll-Like Receptor 4, but Not Neutrophil Extracellular Traps, Promote IFN Type I Expression to Enhance Th2 Responses to Nippostrongylus brasiliensis.
Christophe Pellefigues,Shiau-Choot Tang,Alfonso J Schmidt,Ruby F. White,Olivier Lamiable,Lisa M. Connor,Christiane Ruedl,Jurek Dobrucki,Graham Le Gros,Franca Ronchese +9 more
TL;DR: A limited activation of antibacterial signaling pathways is able to boost antihelminthic responses, suggesting a role for bacterial sensing in the optimal induction of Th2 immunity.
References
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Neutrophil extracellular traps kill bacteria
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TL;DR: This study supports the hypothesis that upper respiratory viral infections are associated with 80-85% of asthma exacerbations in school age children.
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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.
Journal ArticleDOI
Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide.
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.