@article{e27a6676bc0141c399ad27b56942835d,
title = "Transcriptome of airway neutrophils reveals an interferon response in life-threatening respiratory syncytial virus infection",
abstract = "BACKGROUND: Neutrophils are the most abundant cell type infiltrating the airways during severe respiratory syncytial virus (RSV) infection. Their exact role in disease pathophysiology remains enigmatic. Therefore, we determined genome-wide RNA expression profiles of local and systemic neutrophils in RSV bronchiolitis to provide further insight into local neutrophil biology.METHODS: We performed a single-center analysis, in 16 infants, admitted to the pediatric intensive care unit with severe RSV bronchiolitis. Neutrophils were isolated from blood and tracheobronchial aspirates (sputum). After low input RNA sequencing, differential expression of genes was determined followed by gene set analysis.RESULTS: Paired transcriptomic analysis of airway versus blood neutrophils showed an inflammatory phenotype, characterized by NF-kB signaling and upregulated expression of IL-6 and interferon pathways. We observed distinct expression of neutrophil activation genes (TNFSF13B, FCER1G).DISCUSSION: Our data indicate that airway neutrophils regulate their function at the transcriptional level in response to viral infection. It also suggests that local interferon drives the neutrophil response of severe RSV bronchiolitis.",
keywords = "Respiratory syncytial virus, Interferon, Neutrophil, Bronchiolitis, Transcriptome, Sputum, Immunity",
author = "Besteman, {Sjanna B.} and Amie Callaghan and Langedijk, {Annefleur C.} and Hennus, {Marije P.} and Linde Meyaard and Michal Mokry and Bont, {Louis J.} and Calis, {Jorg J.A.}",
note = "Funding Information: This work was supported by an internal UMCU grant of LB. LM is supported by a Vici grant from the Netherlands Organization for Scientific Research (grant no. 91815608).We would like to acknowledge the staff, nurses and doctors, of the pediatric intensive care unit and anesthesiology department of the Wilhelmina's Children Hospital for their help with collection of the samples. Our gratitude goes to the patients and their caregivers for participating in this study. We are thankful to the staff of the flow facility, Pien van der Burght, Jeroen van Velzen and Sebastian van Burgh for their support in sorting the cells, and Eline Harding for support with the clinical data. We thank Marwan Hassani for technical support and Leo Koenderman for critical reading of the manuscript. Funding Information: This work was supported by an internal UMCU grant of LB. LM is supported by a Vici grant from the Netherlands Organization for Scientific Research (grant no. 91815608 ). Publisher Copyright: {\textcopyright} 2020 The Author(s)",
year = "2020",
month = nov,
doi = "10.1016/j.clim.2020.108593",
language = "English",
volume = "220",
pages = "1--10",
journal = "Clinical Immunology",
issn = "1521-6616",
publisher = "Academic Press Inc.",
}