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Differential lower airway dendritic cell patterns may reveal distinct endotypes of RSV bronchiolitis
  1. Aoife Kerrin1,
  2. Paul Fitch1,2,
  3. Claire Errington1,
  4. Dennis Kerr3,
  5. Liz Waxman4,
  6. Kay Riding3,
  7. Jon McCormack3,
  8. Felicity Mehendele3,
  9. Henry McSorley1,
  10. Karen MacKenzie1,
  11. Sabine Wronski5,
  12. Armin Braun5,
  13. Richard Levin4,
  14. Ulf Theilen2,3,
  15. Jürgen Schwarze1,2
  1. 1MRC Centre for Inflammation Research, The University of Edinburgh, Edinburgh, UK
  2. 2Child Life & Health, The University of Edinburgh, Edinburgh, UK
  3. 3Royal Hospital for Sick Children, NHS Lothian, Edinburgh, UK
  4. 4Royal Hospital for Sick Children, NHS Greater Glasgow and Clyde, Glasgow, UK
  5. 5Fraunhofer Institute for Toxicology and Experimental Medicine, Hannover, Germany
  1. Correspondence to Professor Jürgen Schwarze, MD, FRCPCH, Centre for Inflammation Research, Queen's Medical Research Institute, The University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK; jurgen.schwarze{at}ed.ac.uk

Abstract

Rationale 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.

Objective 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.

Methods 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.

Measurements and main results 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.

Conclusions 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.

  • Viral infection
  • Respiratory Infection
  • Paediatric Lung Disaese
  • Innate Immunity

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