RT Journal Article
SR Electronic
T1 β2 integrin LFA1 mediates airway damage following neutrophil trans-epithelial migration during RSV infection
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 1902216
DO 10.1183/13993003.02216-2019
A1 Jenny Amanda Herbert
A1 Yu Deng
A1 Pia Hardelid
A1 Elisabeth Robinson
A1 Luo Ren
A1 Dale Moulding
A1 Rosalind Louise Smyth
A1 Claire Mary Smith
YR 2020
UL http://erj.ersjournals.com/content/early/2020/03/12/13993003.02216-2019.abstract
AB RSV bronchiolitis is the most common cause of infant hospital admissions, but there is limited understanding of the mechanisms of disease and no specific anti-viral treatment. Using a novel in vitro primary trans-epithelial neutrophil migration model and innovative imaging methods, we show that RSV infection of nasal airway epithelium increased neutrophil trans-epithelial migration and adhesion to infected epithelial cells, which is associated with epithelial cell damage, reduced ciliary beat frequency, but also a reduction in infectious viral load.Following migration, RSV infection results in greater neutrophil activation, degranulation and release of neutrophil elastase into the airway surface media compared to neutrophils that migrated across mock-infected nasal epithelial cells. Blocking of the interaction between the ligand on neutrophils (the β2 integrin LFA-1) for intracellular adhesion molecule-1 (ICAM-1) on epithelial cells reduced neutrophil adherence to RSV infected cells and epithelial cell damage to pre-infection levels, but did not reduce the numbers of neutrophils which migrated or prevent the reduction in infectious viral load.These findings have provided important insights into the contribution of neutrophils to airway damage and viral clearance, which are relevant to pathophysiology of RSV bronchiolitis. This model is a convenient, quantitative pre-clinical model that will further elucidate mechanisms that drive disease severity and has utility in anti-viral drug discovery.FootnotesThis manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.Conflict of interest: Dr. Herbert has nothing to disclose.Conflict of interest: Dr. Deng has nothing to disclose.Conflict of interest: Dr. Hardelid has nothing to disclose.Conflict of interest: Dr. Robinson has nothing to disclose.Conflict of interest: Dr. Ren has nothing to disclose.Conflict of interest: Dr. Moulding has nothing to disclose.Conflict of interest: Dr. Smyth has nothing to disclose.Conflict of interest: Dr. Smith has nothing to disclose.