Cysteinyl leukotriene receptor 1 expression identifies a subset of neutrophils during the antiviral response that contributes to postviral atopic airway disease. J Allergy Clin Immunol 2018 Oct;142(4):1206-1217.e5
Date
12/23/2017Pubmed ID
29269317Pubmed Central ID
PMC6005711DOI
10.1016/j.jaci.2017.11.026Scopus ID
2-s2.0-85040679730 (requires institutional sign-in at Scopus site) 25 CitationsAbstract
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.
Author List
Cheung DS, Sigua JA, Simpson PM, Yan K, Hussain SA, Santoro JL, Buell EJ, Hunter DA, Rohlfing M, Patadia D, Grayson MHAuthors
Pippa M. Simpson PhD Adjunct Professor in the Pediatrics department at Medical College of WisconsinKe Yan PhD Associate Professor in the Pediatrics department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AdolescentAdult
Animals
Child
Child, Preschool
Female
Humans
Integrin alpha4
Male
Mice
Middle Aged
Nasal Mucosa
Neutrophils
Receptors, Leukotriene
Respiratory Hypersensitivity
Respiratory Tract Infections
Respirovirus Infections
Sendai virus
Young Adult
