| Literature DB >> 28459437 |
Marie Toussaint1,2, David J Jackson1,2,3,4, Dawid Swieboda1,2, Anabel Guedán1,2, Theodora-Dorita Tsourouktsoglou5, Yee Man Ching1,2, Coraline Radermecker6,7, Heidi Makrinioti1,2, Julia Aniscenko1,2, Nathan W Bartlett1,2, Michael R Edwards1,2, Roberto Solari1,2, Frédéric Farnir7,8, Venizelos Papayannopoulos5, Fabrice Bureau6,7,9, Thomas Marichal6,7, Sebastian L Johnston1,2,3.
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.Entities:
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Year: 2017 PMID： 28459437 PMCID： PMC5821220 DOI： 10.1038/nm.4332
Source DB: PubMed Journal: Nat Med ISSN： 1078-8956 Impact factor: 53.440