Cysteinyl leukotriene receptor 1 expression identifies a subset of neutrophils during the antiviral response that contributes to postviral atopic airway disease - 31/01/18
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Abstract |
Background |
Viral respiratory tract infections increase the risk of development and exacerbation of atopic disease. Previously, we demonstrated the requirement for a neutrophil (PMN) subset expressing CD49d to drive development of postviral atopic airway disease in mice.
Objective |
We sought to determine whether human CD49d+ PMNs are present in the nasal mucosa during acute viral respiratory tract infections and further characterize this PMN subset in human subjects and mice.
Methods |
Sixty subjects (5-50 years old) were enrolled within 4 days of acute onset of upper respiratory symptoms. Nasal lavage for flow cytometry and nasal swabs for viral PCR were performed at enrollment and during convalescence. The Sendai virus mouse model was used to investigate the phenotype and functional relevance of CD49d+ PMNs.
Results |
CD49d+ PMN frequency was significantly higher in nasal lavage fluid during acute respiratory symptoms in all subjects (2.9% vs 1.0%, n = 42, P < .001). In mice CD49d+ PMNs represented a “proatopic” neutrophil subset that expressed cysteinyl leukotriene receptor 1 (CysLTR1) and produced TNF, CCL2, and CCL5. Inhibition of CysLTR1 signaling in the first days of a viral respiratory tract infection was sufficient to reduce accumulation of CD49d+ PMNs in the lungs and development of postviral atopic airway disease. Similar to the mouse, human CD49d+ PMNs isolated from nasal lavage fluid during a viral respiratory tract infection expressed CysLTR1.
Conclusion |
CD49d and CysLTR1–coexpressing PMNs are present during symptoms of an acute viral respiratory tract infection in human subjects. Further study is needed to examine selective targeting of proatopic neutrophils as a potential therapeutic strategy to prevent development of postviral atopic airway disease.
Le texte complet de cet article est disponible en PDF.Graphical abstract |
Key words : Asthma, viral infection, nasal lavage, neutrophils, cysteinyl leukotrienes
Abbreviations used : BAL, cDC, CysLT, CysLTR, FDR, LT, PI, RSV, SeV, sRaw
Plan
| Supported by the National Institutes of Health (grants AI103037 to D.S.C. and HL087778 to M.H.G.), the American Thoracic Society/Merck Translational Research Grant in Asthma (to D.S.C.), the Children's Research Institute of the Children's Hospital of Wisconsin (to M.H.G. and D.S.C.), and the Research Institute at Nationwide Children's Hospital (to M.H.G.). |
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| Disclosure of potential conflict of interest: D. S. Cheung is currently employed by Genentech. M. H. Grayson is a Board member of and received travel funds from the American Board of Allergy & Immunology; received speaking fees from the Kentucky Allergy Society; is the Deputy Editor of Annals of Allergy, Asthma & Immunology; and has received grant support from the Children's Research Institute of the Children's Hospital of Wisconsin, the Research Institute at Nationwide Children's Hospital, Polyphor, and Merck. The rest of the authors declare that they have no relevant conflicts of interest. |
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