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

Respiratory syncytial virus (RSV) is a major cause of pediatric 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 mode...

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Bibliographic Details
Published in:Journal of virology 2020-06, Vol.94 (13)
Main Authors: Deng, Yu, Herbert, Jenny A, Robinson, Elisabeth, Ren, Luo, Smyth, Rosalind L, Smith, Claire M
Format: Article
Language:English
Subjects:
Adult
Cellular Response to Infection
Epithelial Cells - virology
Humans
Neutrophils - immunology
Neutrophils - virology
Primary Cell Culture
Respiratory Mucosa - immunology
Respiratory Mucosa - virology
Respiratory Syncytial Virus Infections - immunology
Respiratory Syncytial Virus Infections - physiopathology
Respiratory Syncytial Virus, Human - physiology
Respiratory Syncytial Viruses - metabolism
Respiratory Syncytial Viruses - pathogenicity
Respiratory Syncytial Viruses - physiology
Virus Diseases - metabolism
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Summary:Respiratory syncytial virus (RSV) is a major cause of pediatric 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 model of the differentiated airway epithelium, we found that the addition of physiological concentrations of neutrophils to RSV-infected nasal cultures was associated with greater epithelial damage with lower ciliary activity, cilium loss, less tight junction expression (ZO-1), and more detachment of epithelial cells than is 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 than in preexposure cultures. Epithelial damage in response to RSV infection was associated with neutrophil activation (within 1 h) and neutrophil degranulation, with significantly greater cellular expression of CD11b and myeloperoxidase and higher levels of neutrophil elastase and myeloperoxidase activity in apical surface media than in media with mock-infected airway epithelial cells (AECs). We also recovered more apoptotic neutrophils from RSV-infected cultures (>40%) than from mock-infected cultures (
ISSN:0022-538X
1098-5514
DOI:10.1128/JVI.02161-19