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
Citations
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The Interplay between Host Immunity and Respiratory Viral Infection in Asthma Exacerbation.
Ferdaus Mohd Altaf Hossain,Ferdaus Mohd Altaf Hossain,Jin Young Choi,Erdenebileg Uyangaa,Seong Ok Park,Seong Kug Eo +5 more
TL;DR: The findings of various in vivo and ex vivo models are discussed to establish the critical heterogenic asthmatic etiologies, host-pathogen relationships, humoral and cell-mediated immune responses, and subsequent mechanisms underlying asthma exacerbation triggered by respiratory viral infections.
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Mobilization and Activation of the Innate Immune Response to Dengue Virus.
TL;DR: The innate inflammatory response to dengue infection is discussed, focusing on the role of evolutionarily conserved innate immune cells, their effector functions, and clinical course.
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Therapeutic Targeting of Neutrophil Extracellular Traps Improves Primary and Secondary Intention Wound Healing in Mice.
Annika Heuer,Carolin Stiel,Julia Elrod,Ingo Königs,Deirdre Vincent,Patrick Schlegel,Magdalena Trochimiuk,Birgit Appl,Konrad Reinshagen,Laia Pagerols Raluy,Michael Boettcher +10 more
TL;DR: In this article, the role of extracellular traps (NETs) and DNase1 on primary and secondary wound healing was examined in 93 C57BL/6 mice, with three different genotypes: wildtype, Pad4-, andDNase1-Knockout (KO).
Journal ArticleDOI
Neutrophil extracellular traps in chronic lung disease: implications for pathogenesis and therapy
Holly R. Keir,James D. Chalmers +1 more
TL;DR: Novel approaches to suppressing NET formation or the associated inflammation are in development and represent an important therapeutic target, and immunomodulating therapies that may reduce inflammatory mediators and NET formation, without compromising bacterial clearance, offer a new treatment path for patients.
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Lung-restricted inhibition of Janus kinase 1 is effective in rodent models of asthma.
Hart S. Dengler,Xiumin Wu,Ivan Peng,Cornelia H. Rinderknecht,Youngsu Kwon,Eric Suto,Pawan Bir Kohli,Marya Liimatta,Kathy Barrett,Julia Lloyd,Gary Cain,Mike Briggs,Stephanie Addo,Gary Salmon,Savita Ubhayakar,Gauri Deshmukh,Sheerin K. Shahidi-Latham,Cristine M. Quiason-Huynh,Janet Jackman,John Liu,Nicholas Charles Ray,Simon Charles Goodacre,Adam R. Johnson,Brent S. McKenzie,Wyne P. Lee,Mark Zak,Jane R. Kenny,Nico Ghilardi +27 more
TL;DR: The data show that local inhibition of Jak1 in the lung can suppress lung inflammation without systemic Jak inhibition in rodents, suggesting that this strategy might be effective for treating asthma.
References
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Neutrophil extracellular traps 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
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