TY - JOUR
T1 - Differential lower airway dendritic cell patterns May reveal distinct endotypes of RSV bronchiolitis
AU - Kerrin, Aoife
AU - Fitch, Paul
AU - Errington, Claire
AU - Kerr, Dennis
AU - Waxman, Liz
AU - Riding, Kay
AU - McCormack, Jon
AU - Mehendele, Felicity
AU - McSorley, Henry
AU - MacKenzie, Karen
AU - Wronski, Sabine
AU - Braun, Armin
AU - Levin, Richard
AU - Theilen, Ulf
AU - Schwarze, Jürgen
PY - 2017/7
Y1 - 2017/7
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84983527173&partnerID=8YFLogxK
U2 - 10.1136/thoraxjnl-2015-207358
DO - 10.1136/thoraxjnl-2015-207358
M3 - Article
C2 - 27531529
AN - SCOPUS:84983527173
SN - 0040-6376
VL - 72
SP - 620
EP - 627
JO - Thorax
JF - Thorax
IS - 7
ER -