期刊
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
卷 142, 期 4, 页码 1206-+出版社
MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2017.11.026
关键词
Asthma; viral infection; nasal lavage; neutrophils; cysteinyl leukotrienes
资金
- National Institutes of Health [AI103037, HL087778]
- American Thoracic Society/Merck Translational Research Grant in Asthma
- Children's Research Institute of the Children's Hospital of Wisconsin
- Research Institute at Nationwide Children's Hospital
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据