Sjanna B Besteman1, Amie Callaghan2, Annefleur C Langedijk3, Marije P Hennus4, Linde Meyaard5, Michal Mokry6, Louis J Bont1, Jorg J A Calis7. 1. Department of Paediatrics, Wilhelmina Children's Hospital, University Medical Centre Utrecht, Utrecht, Lundlaan 6, 3584 EA Utrecht, the Netherlands; Center for Translational Immunology, University Medical Centre Utrecht, Utrecht, Lundlaan 6, 3584 EA Utrecht, the Netherlands. 2. Center for Translational Immunology, University Medical Centre Utrecht, Utrecht, Lundlaan 6, 3584 EA Utrecht, the Netherlands. 3. Department of Paediatrics, Wilhelmina Children's Hospital, University Medical Centre Utrecht, Utrecht, Lundlaan 6, 3584 EA Utrecht, the Netherlands. 4. Department of Paediatric Intensive Care, Wilhelmina Children's Hospital, University Medical Centre Utrecht, Utrecht, Lundlaan 6, 3584 EA Utrecht, the Netherlands. 5. Center for Translational Immunology, University Medical Centre Utrecht, Utrecht, Lundlaan 6, 3584 EA Utrecht, the Netherlands; Oncode Institute, University Medical Centre Utrecht, Utrecht, Lundlaan 6, 3584 EA Utrecht, the Netherlands. 6. Department of cardiology, University Medical Centre Utrecht, Utrecht, Lundlaan 6, 3584 EA Utrecht, the Netherlands. 7. Center for Translational Immunology, University Medical Centre Utrecht, Utrecht, Lundlaan 6, 3584 EA Utrecht, the Netherlands; Department of cardiology, University Medical Centre Utrecht, Utrecht, Lundlaan 6, 3584 EA Utrecht, the Netherlands. Electronic address: j.j.a.calis@umcutrecht.nl.
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.
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 RSVbronchiolitis 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 RSVbronchiolitis. 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 RSVbronchiolitis.
Authors: Sjanna B Besteman; Emily Phung; Henriette H M Raeven; Gimano D Amatngalim; Matevž Rumpret; Juliet Crabtree; Rutger M Schepp; Lisa W Rodenburg; Susanna G Siemonsma; Nile Verleur; Rianne van Slooten; Karen Duran; Gijs W van Haaften; Jeffrey M Beekman; Lauren A Chang; Linde Meyaard; Tjomme van der Bruggen; Guy A M Berbers; Nicole Derksen; Stefan Nierkens; Kaitlyn M Morabito; Tracy J Ruckwardt; Evelyn A Kurt-Jones; Douglas Golenbock; Barney S Graham; Louis J Bont Journal: J Infect Dis Date: 2022-08-24 Impact factor: 7.759
Authors: Clarissa M Koch; Andrew D Prigge; Leah Setar; Kishore R Anekalla; Hahn Chi Do-Umehara; Hiam Abdala-Valencia; Yuliya Politanska; Avani Shukla; Jairo Chavez; Grant R Hahn; Bria M Coates Journal: Front Immunol Date: 2022-09-23 Impact factor: 8.786