CysLTR1-expression identifies a subset of neutrophils during the antiviral response that contributes to post-viral atopic airway disease

Publication date: Available online 18 December 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Dorothy S. Cheung, Jerome A. Sigua, Pippa M. Simpson, Ke Yan, Syed-Rehan A. Hussain, Jennifer L. Santoro, Erika J. Buell, Desire A. Hunter, Michelle Rohlfing, Deepa Patadia, Mitchell H. Grayson
BackgroundRespiratory viral infections increase risk of development and exacerbation of atopic disease. We previously demonstrated the requirement for a neutrophil (PMN) subset expressing CD49d to drive development of post-viral atopic airway disease in mice.ObjectiveTo determine if human CD49d⁺ PMN are present in the nasal mucosa during acute viral respiratory tract infections and further characterize this PMN subset in humans and mice.MethodsSixty subjects (5-50 years old) were enrolled within 4 days of acute onset of upper respiratory symptoms. Nasal lavage for flow cytometry and nasal swab 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⁺ PMN.ResultsCD49d⁺ PMN frequency was significantly higher in the nasal lavage during acute respiratory symptoms in all subjects (2.9% versus 1.0%, n=42, p<0.001). In mice, CD49d⁺ PMN represented a "pro-atopic" neutrophil subset that expressed CysLTR1 and produced TNF, CCL2, and CCL5. Inhibition of CysLTR1 signaling in only the first days of a viral respiratory infection was sufficient to reduce accumulation of CD49d⁺ PMN in the lungs and development of post-viral atopic airway disease. Similar to the mouse, human CD49d⁺ PMN isolated from nasal lavage during a respiratory viral infection expressed CysLTR1.ConclusionCD49d and CysLTR1 co-expressing PMNs are present during symptoms of an acute respiratory viral infections in humans. Further study is needed to examine selective targeting of "pro-atopic" neutrophils as a potential therapeutic strategy to prevent development of post-viral atopic airway disease.

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