Bronchial mucosal Interferon-α/β and pattern recognition receptor expression in experimental rhinovirus-induced asthma exacerbations
File(s)
Author(s)
Type
Journal Article
Abstract
BACKGROUND: The innate immune system senses viral infection via pattern recognition receptors (PRRs) leading to type I interferon (IFN) production: their roles in rhinovirus (RV)-induced asthma exacerbations in vivo are uncertain. OBJECTIVES: To compare bronchial mucosal type I IFN and PRR expression at baseline and following RV infection in atopic asthmatic and control subjects. METHODS: Immunohistochemistry was used to detect expression of IFN-α, IFN-β and the PRRs, toll-like receptor (TLR)-3, melanoma-differentiation-associated gene-5 (MDA-5) and retinoic-acid-inducible protein-I (RIG-I) in bronchial biopsies from 10 atopic asthmatics and 15 non-asthmatic non-atopic controls at baseline and on day four and six weeks following RV infection. RESULTS: We observed IFN-α/β deficiency in bronchial epithelium at three time points in asthma in vivo. Lower epithelial IFN-α/β expression was related to greater virus load, worse airway symptoms, airway hyperresponsiveness (AHR) and reductions in lung function during RV infection. We found lower frequencies of bronchial subepithelial monocytes/macrophages expressing IFN-α/β in asthma during infection. IFN deficiency at baseline was not accompanied by deficient PRR expression in asthma. Both epithelial and subepithelial PRR expression was induced during RV infection. RV infection increased numbers of subepithelial IFN/PRRs-expressing inflammatory cells were related to greater virus load, AHR and reductions in lung function. CONCLUSIONS: Bronchial epithelial IFN-α/β expression and numbers of subepithelial IFN-α/β-expressing monocytes/macrophages during infection were both deficient in asthma. Lower epithelial IFN-α/β expression was associated with adverse clinical outcomes following RV infection in vivo. Increases in subepithelial cells expressing IFN/PRRs during infection were also related to greater virus load/illness severity.
Date Issued
2019-01-01
Date Acceptance
2018-04-03
Citation
Journal of Allergy and Clinical Immunology, 2019, 143 (1), pp.114-125.e4
ISSN
0091-6749
Publisher
Elsevier
Start Page
114
End Page
125.e4
Journal / Book Title
Journal of Allergy and Clinical Immunology
Volume
143
Issue
1
Copyright Statement
© 2018 The Authors. Published by Elsevier Inc. on behalf of the American Academy of
Allergy, Asthma & Immunology. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Allergy, Asthma & Immunology. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Sponsor
Medical Research Council (MRC)
National Institute for Health Research
Asthma UK
Asthma UK
Medical Research Council (MRC)
Commission of the European Communities
Medical Research Council (MRC)
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/29698627
PII: S0091-6749(18)30610-9
Grant Number
G0601236
NF-SI-0514-10092
CH11SJ
CH11SJ
G1000758
233015
G1000758
Subjects
Asthma exacerbation
pattern recognition receptors
rhinovirus infection
type I interferon
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2018-04-24