TY - JOUR
T1 - Type I conventional dendritic cells relate to disease severity in virus-induced asthma exacerbations
AU - MRC-GSK Strategic Alliance Consortium
AU - Cameron, Aoife
AU - Dhariwal, Jaideep
AU - Upton, Nadine
AU - Ranz Jimenez, Ismael
AU - Paulsen, Malte
AU - Wong, Ernie
AU - Trujillo-Torralbo, Maria Belen
AU - Del Rosario, Ajerico
AU - Jackson, David J.
AU - Edwards, Michael R.
AU - Johnston, Sebastian L.
AU - Walton, Ross P.
N1 - Funding Information:
This work was supported by a Medical Research Council (MRC) and GlaxoSmithKline Strategic Alliance Programme Grant number G1100238, the National Institute of Health Research (NIHR) Biomedical Research Centre funding scheme and the MRC and Asthma UK Centre Grant G1000758. SLJ is the Asthma UK Clinical Chair (grant CH11SJ) and is an Emeritus NIHR Senior Investigator.
Funding Information:
This work was supported by a Medical Research Council (MRC) and GlaxoSmithKline Strategic Alliance Programme Grant number G1100238, the National Institute of Health Research (NIHR) Biomedical Research Centre funding scheme and the MRC and Asthma UK Centre Grant G1000758. SLJ is the Asthma UK Clinical Chair (grant CH11SJ) and is an Emeritus NIHR Senior Investigator. The authors thank the St Mary’s Flow Cytometry Core Facility, National Heart and Lung Institute, Imperial College London for support and access to equipment.
Publisher Copyright:
© 2022 The Authors. Clinical & Experimental Allergy published by John Wiley & Sons Ltd.
PY - 2022/3/31
Y1 - 2022/3/31
N2 - RATIONALE: Rhinoviruses are the major precipitant of asthma exacerbations and individuals with asthma experience more severe/prolonged rhinovirus infections. Concurrent viral infection and allergen exposure synergistically increase exacerbation risk. Although dendritic cells orchestrate immune responses to both virus and allergen, little is known about their role in viral asthma exacerbations. OBJECTIVES: To characterize dendritic cell populations present in the lower airways, and to assess whether their numbers are altered in asthma compared to healthy subjects prior to infection and during rhinovirus-16 infection. METHODS: Moderately-severe atopic asthmatic patients and healthy controls were experimentally infected with rhinovirus-16. Bronchoalveolar lavage was collected at baseline, day 3 and day 8 post infection and dendritic cells isolated using fluorescence activated cell sorting. MEASUREMENTS AND MAIN RESULTS: Numbers of type I conventional dendritic cells, which cross prime CD8+ T helper cells and produce innate interferons, were significantly reduced in the lower airways of asthma patients compared to healthy controls at baseline. This reduction was associated serum IgE at baseline and with reduced numbers of CD8+ T helper cells and with increased viral replication, airway eosinophils and reduced lung function during infection. IgE receptor expression on lower airway plasmacytoid dendritic cells was significantly increased in asthma, consistent with a reduced capacity to produce innate interferons. CONCLUSIONS: Reduced numbers of anti-viral type I conventional dendritic cells in asthma are associated with adverse outcomes during rhinovirus infection. This, with increased FcεR1α expression on lower airway plasmacytoid DCs could mediate the more permissive respiratory viral infection observed in asthma patients.
AB - RATIONALE: Rhinoviruses are the major precipitant of asthma exacerbations and individuals with asthma experience more severe/prolonged rhinovirus infections. Concurrent viral infection and allergen exposure synergistically increase exacerbation risk. Although dendritic cells orchestrate immune responses to both virus and allergen, little is known about their role in viral asthma exacerbations. OBJECTIVES: To characterize dendritic cell populations present in the lower airways, and to assess whether their numbers are altered in asthma compared to healthy subjects prior to infection and during rhinovirus-16 infection. METHODS: Moderately-severe atopic asthmatic patients and healthy controls were experimentally infected with rhinovirus-16. Bronchoalveolar lavage was collected at baseline, day 3 and day 8 post infection and dendritic cells isolated using fluorescence activated cell sorting. MEASUREMENTS AND MAIN RESULTS: Numbers of type I conventional dendritic cells, which cross prime CD8+ T helper cells and produce innate interferons, were significantly reduced in the lower airways of asthma patients compared to healthy controls at baseline. This reduction was associated serum IgE at baseline and with reduced numbers of CD8+ T helper cells and with increased viral replication, airway eosinophils and reduced lung function during infection. IgE receptor expression on lower airway plasmacytoid dendritic cells was significantly increased in asthma, consistent with a reduced capacity to produce innate interferons. CONCLUSIONS: Reduced numbers of anti-viral type I conventional dendritic cells in asthma are associated with adverse outcomes during rhinovirus infection. This, with increased FcεR1α expression on lower airway plasmacytoid DCs could mediate the more permissive respiratory viral infection observed in asthma patients.
KW - atopy
KW - DC
KW - rhinovirus
UR - http://www.scopus.com/inward/record.url?scp=85127402493&partnerID=8YFLogxK
U2 - 10.1111/cea.14116
DO - 10.1111/cea.14116
M3 - Article
C2 - 35212067
AN - SCOPUS:85127402493
SN - 0954-7894
VL - 52
SP - 550
EP - 560
JO - Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology
JF - Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology
IS - 4
ER -