Bronchial mucosal Interferon-α/β and pattern recognition receptor expression in experimental rhinovirus-induced asthma exacerbations

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Title: Bronchial mucosal Interferon-α/β and pattern recognition receptor expression in experimental rhinovirus-induced asthma exacerbations
Authors: Zhu, J
Message, SD
Mallia, P
Kebadze, T
Contoli, M
Ward, CK
Barnathan, ES
Mascelli, MA
Kon, OM
Papi, A
Stanciu, LA
Edwards, MR
Jeffery, PK
Johnston, SL
Item 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.
Issue Date: 1-Jan-2019
Date of Acceptance: 3-Apr-2018
URI: http://hdl.handle.net/10044/1/58898
DOI: https://doi.org/10.1016/j.jaci.2018.04.003
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/).
Sponsor/Funder: 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)
Funder's Grant Number: G0601236
NF-SI-0514-10092
CH11SJ
CH11SJ
G1000758
233015
G1000758
Keywords: Science & Technology
Life Sciences & Biomedicine
Allergy
Immunology
Asthma exacerbation
rhinovirus infection
type I interferon
pattern recognition receptors
DOUBLE-STRANDED-RNA
EPITHELIAL-CELLS
AIRWAY INFLAMMATION
TYPE-2 INFLAMMATION
VIRAL-INFECTIONS
RIG-I
DEFICIENT
INTERFERONS
VIRUS
BETA
Asthma exacerbation
pattern recognition receptors
rhinovirus infection
type I interferon
Asthma exacerbation
pattern recognition receptors
rhinovirus infection
type I interferon
Allergy
1107 Immunology
Publication Status: Published
Conference Place: United States
Online Publication Date: 2018-04-24
Appears in Collections:National Heart and Lung Institute
Airway Disease
Faculty of Medicine



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