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Trans-epithelial migration is essential for neutrophil activation during RSV infection

Robinson, Elisabeth; Herbert, Jenny Amanda; Palor, Machaela; Ren, Luo; Larken, Isobel; Patel, Alisha; Moulding, Dale; ... Smith, Claire Mary; + view all (2023) Trans-epithelial migration is essential for neutrophil activation during RSV infection. Journal of Leukocyte Biology 10.1093/jleuko/qiad011. (In press). Green open access

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Abstract

The recruitment of neutrophils to the infected airway occurs early following respiratory syncytial virus (RSV) infection and high numbers of activated neutrophils in airway and blood is associated with the development of severe disease. The aim of this study was to investigate whether trans-epithelial migration is sufficient and necessary for neutrophil activation during RSV infection. Here, we used flow cytometry and novel live-cell fluorescent microscopy to track neutrophil movement during trans-epithelial migration and measure the expression of key activation markers in a human model of RSV infection. We found that when migration occurred, neutrophil expression of CD11b, CD62L, CD64, NE and MPO increased. However, the same increase did not occur on basolateral neutrophils when neutrophils were prevented from migrating, suggesting that activated neutrophils reverse migrate from the airway to the bloodstream side, as has been suggested by clinical observations. We then combined our findings with the temporal and spatial profiling and suggest three initial phases of neutrophil recruitment and behaviour in the airways during RSV infection; 1) initial chemotaxis; 2) neutrophil activation and reverse migration; 3) amplified chemotaxis and clustering, all of which occur within 20 minutes. This work and the novel outputs could be used to develop therapeutics and provide new insight into how neutrophil activation and a dysregulated neutrophil response to RSV mediates disease severity.

Type: Article
Title: Trans-epithelial migration is essential for neutrophil activation during RSV infection
Open access status: An open access version is available from UCL Discovery
DOI: 10.1093/jleuko/qiad011
Publisher version: https://doi.org/10.1093/jleuko/qiad011
Language: English
Additional information: © The Author(s) 2023. Published by Oxford University Press on behalf of Society for Leukocyte Biology. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: virus infection, bronchiolitis, airway epithelial cells, migration, movement, neutrophils
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/10164355
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