Reduced nasal viral load and IFN responses in infants with RSV bronchiolitis and respiratory failure
File(s)
Author(s)
Type
Journal Article
Abstract
RATIONALE: Respiratory syncytial virus (RSV) bronchiolitis is a major cause of morbidity and mortality in infancy. Severe disease is thought to result from uncontrolled viral replication, an excessive immune response, or both. OBJECTIVES: To determine RSV load and immune mediator levels in nasal mucosal lining fluid by serial sampling of nasal fluids from cases of moderate and severe bronchiolitis over the course of infection. METHODS: Infants with viral bronchiolitis necessitating admission (n=55) were recruited from a paediatric centre during 2016/17. Of these, 30 were RSV infected (18 'moderate', and 12 mechanically ventilated 'severe'). Nasal fluids were sampled frequently over time using nasosorption devices and nasophayngeal aspiration (NPA). Hierarchical clustering of time weighted averages (TWA) was performed to investigate cytokine and chemokine levels, and gene expression profiling was conducted. MEASUREMENTS AND MAIN RESULTS: Unexpectedly, cases of severe RSV bronchiolitis had lower nasal viral loads and reduced interferon (IFN)-γ and CCL5/RANTES levels compared to those with moderate disease, especially when allowance was made for disease duration (all P<0.05). Reduced cytokine/chemokine levels in severe disease were also seen in children with other viral infections. Gene expression analysis of NPA samples (n=43) confirmed reduced type-I IFN gene expression in severe bronchiolitis accompanied by enhanced expression of MUC5AC and IL17A. CONCLUSIONS: Infants with severe RSV bronchiolitis have lower nasal viral load, IP-10/CXCL10 and type-I IFNs levels compared to moderately ill children, but enhanced MUC5AC and IL17A gene expression in nasal cells.
Date Issued
2018-04-24
Date Acceptance
2018-04-23
Citation
American Journal of Respiratory and Critical Care Medicine, 2018, 198 (8), pp.1074-1084
ISSN
1073-449X
Publisher
American Thoracic Society
Start Page
1074
End Page
1084
Journal / Book Title
American Journal of Respiratory and Critical Care Medicine
Volume
198
Issue
8
Copyright Statement
© 2018 by the American Thoracic Society.
Sponsor
Imperial College Healthcare NHS Trust- BRC Funding
National Institute for Health Research
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/29688024
Grant Number
RDA02
NF-SI-0513-10150
Subjects
innate immunity
interferon
nasosorption
respiratory syncytial virus
viral bronchiolitis
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2018-04-24