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Neutrophil-Airway Epithelial Interactions Result in Increased Epithelial Damage and Viral Clearance during Respiratory Syncytial Virus Infection

Deng, Y; Herbert, JA; Robinson, E; Ren, L; Smyth, RL; Smith, CM; (2020) Neutrophil-Airway Epithelial Interactions Result in Increased Epithelial Damage and Viral Clearance during Respiratory Syncytial Virus Infection. Journal of Virology , 94 (13) , Article e02161-19. 10.1128/JVI.02161-19. Green open access

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Abstract

Respiratory syncytial virus (RSV) is a major cause of paediatric respiratory disease. Large numbers of neutrophils are recruited into the airways of children with severe RSV disease. It is not clear whether or how neutrophils enhance recovery from disease or contribute to its pathology.Using an in vitro model of the differentiated airway epithelium, we found that addition of physiological concentrations of neutrophils to RSV infected nasal cultures was associated with greater epithelial damage with lower ciliary activity, cilia loss, less tight junction expression (ZO-1) and more detachment of epithelial cells than seen with RSV infection alone. This was also associated with a decrease in infectious virus and fewer RSV positive cells in cultures after neutrophil exposure compared to pre-exposure. Epithelial damage in response to RSV infection was associated with neutrophil activation (within 1h), and neutrophil degranulation with significantly greater cellular expression of CD11b, MPO and higher neutrophil elastase and myeloperoxidase activity in apical surface medias compared to that from mock-infected AECs. We also recovered more apoptotic neutrophils from RSV infected cultures (>40%), compared to <5% in mock infected cultures after 4h.The results of this study could provide important insights into the role of neutrophils in host response in the airway.Importance: This study shows that the RSV infected human airway drives changes in the behaviour of human neutrophils including increasing activation markers and delaying apoptosis that results in greater airway damage and viral clearance.

Type: Article
Title: Neutrophil-Airway Epithelial Interactions Result in Increased Epithelial Damage and Viral Clearance during Respiratory Syncytial Virus Infection
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1128/JVI.02161-19
Publisher version: https://doi.org/10.1128/JVI.02161-19
Language: English
Additional information: Copyright © 2020 Deng et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/).
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept
URI: https://discovery.ucl.ac.uk/id/eprint/10095369
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