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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Journal ArticleDOI
Neutrophil Extracellular Traps in Asthma: Friends or Foes?
TL;DR: The role of neutrophils and their mediators in different asthma phenotypes are largely unknown as mentioned in this paper , and the potential of extracellular traps (NETs) in asthma is discussed.
Journal ArticleDOI
Simvastatin Reduces NETosis to Attenuate Severe Asthma by Inhibiting PAD4 Expression
TL;DR: In this paper , Simvastatin was used to attenuate severe asthma by reducing neutrophil extracellular traps (NETs), which play a crucial role in severe asthma.
Journal ArticleDOI
Casting a wide NET: an update on uncontrolled NETosis in response to COVID-19 infection
TL;DR: In this paper , the progress that has been made in regards to the ideas postulated by the perspective will be discussed, with a focus on the therapeutics that target neutrophil extracellular trap (NET) formation.
Book ChapterDOI
Methods to Detect Neutrophil Extracellular Traps in Asthma.
TL;DR: In this paper , the authors describe methods to quantify NETs in BALF, namely the quantification of cell-free DNA, or of myeloperoxidase (MPO) or neutrophil elastase (NE) complexed with cell free DNA.
Journal ArticleDOI
Pulmonary Eosinophils at the Center of the Allergic Space-Time Continuum
TL;DR: In this article, the authors argue that immunological differences in eosinophils are a function of time and space as the allergic inflammatory response is initiated and resolved, and outline the inflammatory time line of allergic airway inflammation from acute, late, adaptive to chronic processes.
References
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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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Community study of role of viral infections in exacerbations of asthma in 9-11 year old children.
Sebastian L. Johnston,Philip Pattemore,G. Sanderson,Sandra Smith,F Lampe,Lynn Josephs,P. Symington,S. O'Toole,S. H. Myint,D. A. J. Tyrrell +9 more
TL;DR: This study supports the hypothesis that upper respiratory viral infections are associated with 80-85% of asthma exacerbations in school age children.
Journal ArticleDOI
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.