title: Differential lower airway dendritic cell patterns may reveal distinct endotypes of RSV bronchiolitis.
abstract: The pathogenesis of respiratory syncytial virus (RSV) bronchiolitis in infants remains poorly understood. Mouse models implicate pulmonary T cells in the development of RSV disease. T cell responses are initiated by dendritic cells (DCs), which accumulate in lungs of RSV-infected mice. In infants with RSV bronchiolitis, previous reports have shown that DCs are mobilised to the nasal mucosa, but data on lower airway DC responses are lacking.
  
  
  
  To determine the presence and phenotype of DCs and associated immune cells in bronchoalveolar lavage (BAL) and peripheral blood samples from infants with RSV bronchiolitis.
  
  
  
  Infants intubated and ventilated due to severe RSV bronchiolitis or for planned surgery (controls with healthy lungs) underwent non-bronchoscopic BAL. Immune cells in BAL and blood samples were characterised by flow cytometry and cytokines measured by Human V-Plex Pro-inflammatory Panel 1 MSD kit.
  
  
  
  In RSV cases, BAL conventional DCs (cDCs), NK T cells, NK cells and pro-inflammatory cytokines accumulated, plasmacytoid DCs (pDCs) and T cells were present, and blood cDCs increased activation marker expression. When stratifying RSV cases by risk group, preterm and older (≥4 months) infants had fewer BAL pDCs than term born and younger (<4 months) infants, respectively.
  
  
  
  cDCs accumulate in the lower airways during RSV bronchiolitis, are activated systemically and may, through activation of T cells, NK T cells and NK cells, contribute to RSV-induced inflammation and disease. In addition, the small population of airway pDCs in preterm and older infants may reveal a distinct endotype of RSV bronchiolitis with weak antiviral pDC responses.
authors.affiliation: MRC Centre for Inflammation Research, The University of Edinburgh, Edinburgh, UK.
authors.forename: Aoife
authors.initials: A
authors.lastname: Kerrin
authors.affiliation: MRC Centre for Inflammation Research, The University of Edinburgh, Edinburgh, UK.|Child Life & Health, The University of Edinburgh, Edinburgh, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Fitch
authors.affiliation: MRC Centre for Inflammation Research, The University of Edinburgh, Edinburgh, UK.
authors.forename: Claire
authors.initials: C
authors.lastname: Errington
authors.affiliation: Royal Hospital for Sick Children, NHS Lothian, Edinburgh, UK.
authors.forename: Dennis
authors.initials: D
authors.lastname: Kerr
authors.affiliation: Royal Hospital for Sick Children, NHS Greater Glasgow and Clyde, Glasgow, UK.
authors.forename: Liz
authors.initials: L
authors.lastname: Waxman
authors.affiliation: Royal Hospital for Sick Children, NHS Lothian, Edinburgh, UK.
authors.forename: Kay
authors.initials: K
authors.lastname: Riding
authors.affiliation: Royal Hospital for Sick Children, NHS Lothian, Edinburgh, UK.
authors.forename: Jon
authors.initials: J
authors.lastname: McCormack
authors.affiliation: Royal Hospital for Sick Children, NHS Lothian, Edinburgh, UK.
authors.forename: Felicity
authors.initials: F
authors.lastname: Mehendele
authors.affiliation: MRC Centre for Inflammation Research, The University of Edinburgh, Edinburgh, UK.
authors.forename: Henry
authors.initials: H
authors.lastname: McSorley
authors.affiliation: MRC Centre for Inflammation Research, The University of Edinburgh, Edinburgh, UK.
authors.forename: Karen
authors.initials: K
authors.lastname: MacKenzie
authors.affiliation: Fraunhofer Institute for Toxicology and Experimental Medicine, Hannover, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Wronski
authors.affiliation: Fraunhofer Institute for Toxicology and Experimental Medicine, Hannover, Germany.
authors.forename: Armin
authors.initials: A
authors.lastname: Braun
authors.affiliation: Royal Hospital for Sick Children, NHS Greater Glasgow and Clyde, Glasgow, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Levin
authors.affiliation: Child Life & Health, The University of Edinburgh, Edinburgh, UK.|Royal Hospital for Sick Children, NHS Lothian, Edinburgh, UK.
authors.forename: Ulf
authors.initials: U
authors.lastname: Theilen
authors.affiliation: MRC Centre for Inflammation Research, The University of Edinburgh, Edinburgh, UK.|Child Life & Health, The University of Edinburgh, Edinburgh, UK.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Schwarze
mesh_terms: D000367:Age Factors; D015703:Antigens, CD / Q000097:blood; D001990:Bronchiolitis, Viral / Q000097:blood / Q000276:immunology* / Q000821:virology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology* / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes; D019013:CD40 Antigens / Q000097:blood; D018414:CD8-Positive T-Lymphocytes; D016022:Case-Control Studies; D002452:Cell Count; D016207:Cytokines / Q000032:analysis* / Q000097:blood; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D006801:Humans; D007136:Immunoglobulins / Q000097:blood; D007223:Infant; D007231:Infant, Newborn; D007694:Killer Cells, Natural; D008264:Macrophages; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood; D009000:Monocytes; D055611:Natural Killer T-Cells; D010641:Phenotype; D047928:Premature Birth / Q000276:immunology; D018357:Respiratory Syncytial Virus Infections / Q000150:complications*; D047929:Term Birth / Q000276:immunology; D000097802:CD83 Antigen
chemical_list: D015703:Antigens, CD; D019013:CD40 Antigens; D016207:Cytokines; D007136:Immunoglobulins; D008562:Membrane Glycoproteins; D000097802:CD83 Antigen
keywords: Innate Immunity; Paediatric Lung Disaese; Respiratory Infection; Viral infection