Journal
NATURE MEDICINE
Volume 23, Issue 6, Pages 681-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nm.4332
Keywords
-
Funding
- Wallonie-Bruxelles International organization
- European Academy of Allergy and Clinical Immunology
- Acteria Foundation
- European Research Council (ERC FP7 grant) [233015]
- Chair from Asthma UK [CH11SJ]
- Medical Research Council Centre [G1000758]
- National Institute of Health Research (NIHR) Biomedical Research Centre [P26095]
- Predicta FP7 Collaborative Project [260895]
- NIHR Biomedical Research Centre at Imperial College London
- Asthma UK [05/067, 06/050, 08/048, MRC-AsthmaUKCentre, CH11SJ, MRC-Asthma UK Centre] Funding Source: researchfish
- Medical Research Council [G1100168, MR/L012693/1, G1100238, MC_PC_11005, G1000758, G1000758B, G0601236, G0601369, G0600879] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0508-10212, NF-SI-0514-10092] Funding Source: researchfish
- Rosetrees Trust [M422] Funding Source: researchfish
- The Francis Crick Institute [10129] Funding Source: researchfish
- MRC [G0601236, G1100238, G0600879, G1100168, G0601369, MR/L012693/1, MC_PC_11005] Funding Source: UKRI
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available