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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References
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Essential Role of Lung Plasmacytoid Dendritic Cells in Preventing Asthmatic Reactions to Harmless Inhaled Antigen
Hendrik Jan de Heer,Hamida Hammad,Thomas Soullié,Daniëlle Hijdra,Nanda Vos,Monique Willart,Henk C. Hoogsteden,Bart N. Lambrecht +7 more
TL;DR: It is shown that both myeloid and plasmacytoid DCs take up inhaled antigen in the lung and present it in an immunogenic or tolerogenic form to draining node T cells, showing intrinsic protection against inflammatory responses to harmless antigen.
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Conventional and Monocyte-Derived CD11b+ Dendritic Cells Initiate and Maintain T Helper 2 Cell-Mediated Immunity to House Dust Mite Allergen
Maud Plantinga,Martin Guilliams,Martin Guilliams,Manon Vanheerswynghels,Kim Deswarte,Filipe Branco-Madeira,Wendy Toussaint,Leen Vanhoutte,Leen Vanhoutte,Katrijn Neyt,Nigel Killeen,Bernard Malissen,Hamida Hammad,Bart N. Lambrecht,Bart N. Lambrecht +14 more
TL;DR: Migratory CD11b(+) cDCs are identified as the principal subset inducing Th2 cell-mediated immunity in the LN, whereas moDCs orchestrate allergic inflammation in the lung.
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Diabetes primes neutrophils to undergo NETosis, which impairs wound healing
Siu Ling Wong,Melanie Demers,Kimberly Martinod,Maureen Gallant,Yanming Wang,Allison B. Goldfine,C. Ronald Kahn,Denisa D. Wagner +7 more
TL;DR: It is shown that neutrophils isolated from type 1 and type 2 diabetic humans and mice were primed to produce NETs (a process termed NETosis), and wound healing was accelerated in Padi4−/− mice as compared to WT mice, and it was not compromised by diabetes.
Journal ArticleDOI
Neutrophils sense microbe size and selectively release neutrophil extracellular traps in response to large pathogens
Nora Branzk,Aleksandra Lubojemska,Sarah E. Hardison,Qian Wang,Maximiliano G. Gutierrez,Gordon D. Brown,Venizelos Papayannopoulos +6 more
TL;DR: It is found that neutrophils sensed microbe size and selectively released neutrophil extracellular traps (NETs) in response to large pathogens, such as Candida albicans hyphae andextracellular aggregates of Mycobacterium bovis, but not inresponse to small yeast or single bacteria.
Journal ArticleDOI
NETosis: how vital is it?
Bryan G. Yipp,Paul Kubes +1 more
TL;DR: The evidence that neutrophil extracellular traps (NETs) play a critical role in innate immunity is examined and how infections are related to the development of autoimmune and vasculitic diseases through unintended but detrimental bystander damage resulting from NET release is examined.