Airway Epithelial Cell Immunity Is Delayed During Rhinovirus Infection in Asthma and COPD
Respiratory viral infections, particularly those caused by rhinovirus, exacerbate chronic respiratory inflammatory diseases, such as asthma and chronic obstructive pulmonary disease (COPD). Airway epithelial cells are the primary site of rhinovirus replication and responsible of initiating the host...
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Frontiers Media S.A.
2020-05-01
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Series: | Frontiers in Immunology |
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Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2020.00974/full |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Punnam Chander Veerati Punnam Chander Veerati Niamh M. Troy Andrew T. Reid Andrew T. Reid Ngan Fung Li Ngan Fung Li Kristy S. Nichol Kristy S. Nichol Parwinder Kaur Steven Maltby Steven Maltby Peter A. B. Wark Peter A. B. Wark Peter A. B. Wark Darryl A. Knight Darryl A. Knight Darryl A. Knight Darryl A. Knight Anthony Bosco Chris L. Grainge Chris L. Grainge Chris L. Grainge Nathan W. Bartlett Nathan W. Bartlett |
spellingShingle |
Punnam Chander Veerati Punnam Chander Veerati Niamh M. Troy Andrew T. Reid Andrew T. Reid Ngan Fung Li Ngan Fung Li Kristy S. Nichol Kristy S. Nichol Parwinder Kaur Steven Maltby Steven Maltby Peter A. B. Wark Peter A. B. Wark Peter A. B. Wark Darryl A. Knight Darryl A. Knight Darryl A. Knight Darryl A. Knight Anthony Bosco Chris L. Grainge Chris L. Grainge Chris L. Grainge Nathan W. Bartlett Nathan W. Bartlett Airway Epithelial Cell Immunity Is Delayed During Rhinovirus Infection in Asthma and COPD Frontiers in Immunology rhinovirus interferon response innate immunity asthma chronic obstructive pulmonary disease (COPD) air-liquid interface (ALI) culture |
author_facet |
Punnam Chander Veerati Punnam Chander Veerati Niamh M. Troy Andrew T. Reid Andrew T. Reid Ngan Fung Li Ngan Fung Li Kristy S. Nichol Kristy S. Nichol Parwinder Kaur Steven Maltby Steven Maltby Peter A. B. Wark Peter A. B. Wark Peter A. B. Wark Darryl A. Knight Darryl A. Knight Darryl A. Knight Darryl A. Knight Anthony Bosco Chris L. Grainge Chris L. Grainge Chris L. Grainge Nathan W. Bartlett Nathan W. Bartlett |
author_sort |
Punnam Chander Veerati |
title |
Airway Epithelial Cell Immunity Is Delayed During Rhinovirus Infection in Asthma and COPD |
title_short |
Airway Epithelial Cell Immunity Is Delayed During Rhinovirus Infection in Asthma and COPD |
title_full |
Airway Epithelial Cell Immunity Is Delayed During Rhinovirus Infection in Asthma and COPD |
title_fullStr |
Airway Epithelial Cell Immunity Is Delayed During Rhinovirus Infection in Asthma and COPD |
title_full_unstemmed |
Airway Epithelial Cell Immunity Is Delayed During Rhinovirus Infection in Asthma and COPD |
title_sort |
airway epithelial cell immunity is delayed during rhinovirus infection in asthma and copd |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2020-05-01 |
description |
Respiratory viral infections, particularly those caused by rhinovirus, exacerbate chronic respiratory inflammatory diseases, such as asthma and chronic obstructive pulmonary disease (COPD). Airway epithelial cells are the primary site of rhinovirus replication and responsible of initiating the host immune response to infection. Numerous studies have reported that the anti-viral innate immune response (including type I and type III interferon) in asthma is less effective or deficient leading to the conclusion that epithelial innate immunity is a key determinant of disease severity during a rhinovirus induced exacerbation. However, deficient rhinovirus-induced epithelial interferon production in asthma has not always been observed. We hypothesized that disparate in vitro airway epithelial infection models using high multiplicity of infection (MOI) and lacking genome-wide, time course analyses have obscured the role of epithelial innate anti-viral immunity in asthma and COPD. To address this, we developed a low MOI rhinovirus model of differentiated primary epithelial cells obtained from healthy, asthma and COPD donors. Using genome-wide gene expression following infection, we demonstrated that gene expression patterns are similar across patient groups, but that the kinetics of induction are delayed in cells obtained from asthma and COPD donors. Rhinovirus-induced innate immune responses were defined by interferons (type-I, II, and III), interferon response factors (IRF1, IRF3, and IRF7), TLR signaling and NF-κB and STAT1 activation. Induced gene expression was evident at 24 h and peaked at 48 h post-infection in cells from healthy subjects. In contrast, in cells from donors with asthma or COPD induction was maximal at or beyond 72–96 h post-infection. Thus, we propose that propensity for viral exacerbations of asthma and COPD relate to delayed (rather than deficient) expression of epithelial cell innate anti-viral immune genes which in turns leads to a delayed and ultimately more inflammatory host immune response. |
topic |
rhinovirus interferon response innate immunity asthma chronic obstructive pulmonary disease (COPD) air-liquid interface (ALI) culture |
url |
https://www.frontiersin.org/article/10.3389/fimmu.2020.00974/full |
work_keys_str_mv |
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doaj-4faa7dffe0d2434483b725cb07285cb02020-11-25T03:33:49ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-05-011110.3389/fimmu.2020.00974533192Airway Epithelial Cell Immunity Is Delayed During Rhinovirus Infection in Asthma and COPDPunnam Chander Veerati0Punnam Chander Veerati1Niamh M. Troy2Andrew T. Reid3Andrew T. Reid4Ngan Fung Li5Ngan Fung Li6Kristy S. Nichol7Kristy S. Nichol8Parwinder Kaur9Steven Maltby10Steven Maltby11Peter A. B. Wark12Peter A. B. Wark13Peter A. B. Wark14Darryl A. Knight15Darryl A. Knight16Darryl A. Knight17Darryl A. Knight18Anthony Bosco19Chris L. Grainge20Chris L. Grainge21Chris L. Grainge22Nathan W. Bartlett23Nathan W. Bartlett24School of Medicine and Public Health, University of Newcastle, Callaghan, NSW, AustraliaPriority Research Centre for Healthy Lungs, Hunter Medical Research Institute, University of Newcastle, New Lambton Heights, NSW, AustraliaSystems Immunology, Telethon Kids Institute, University of Western Australia, Perth, WA, AustraliaSchool of Medicine and Public Health, University of Newcastle, Callaghan, NSW, AustraliaPriority Research Centre for Healthy Lungs, Hunter Medical Research Institute, University of Newcastle, New Lambton Heights, NSW, AustraliaPriority Research Centre for Healthy Lungs, Hunter Medical Research Institute, University of Newcastle, New Lambton Heights, NSW, AustraliaSchool of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, NSW, AustraliaSchool of Medicine and Public Health, University of Newcastle, Callaghan, NSW, AustraliaPriority Research Centre for Healthy Lungs, Hunter Medical Research Institute, University of Newcastle, New Lambton Heights, NSW, AustraliaUWA School of Agriculture and Environment, Faculty of Science, The University of Western Australia, Perth, WA, AustraliaPriority Research Centre for Healthy Lungs, Hunter Medical Research Institute, University of Newcastle, New Lambton Heights, NSW, AustraliaSchool of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, NSW, AustraliaSchool of Medicine and Public Health, University of Newcastle, Callaghan, NSW, AustraliaPriority Research Centre for Healthy Lungs, Hunter Medical Research Institute, University of Newcastle, New Lambton Heights, NSW, AustraliaDepartment of Respiratory and Sleep Medicine, John Hunter Hospital, New Lambton Heights, NSW, AustraliaPriority Research Centre for Healthy Lungs, Hunter Medical Research Institute, University of Newcastle, New Lambton Heights, NSW, AustraliaSchool of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, NSW, AustraliaDepartment of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, BC, CanadaResearch and Academic Affairs, Providence Health Care Research Institute, Vancouver, BC, CanadaSystems Immunology, Telethon Kids Institute, University of Western Australia, Perth, WA, AustraliaSchool of Medicine and Public Health, University of Newcastle, Callaghan, NSW, AustraliaPriority Research Centre for Healthy Lungs, Hunter Medical Research Institute, University of Newcastle, New Lambton Heights, NSW, AustraliaDepartment of Respiratory and Sleep Medicine, John Hunter Hospital, New Lambton Heights, NSW, AustraliaPriority Research Centre for Healthy Lungs, Hunter Medical Research Institute, University of Newcastle, New Lambton Heights, NSW, AustraliaSchool of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, NSW, AustraliaRespiratory viral infections, particularly those caused by rhinovirus, exacerbate chronic respiratory inflammatory diseases, such as asthma and chronic obstructive pulmonary disease (COPD). Airway epithelial cells are the primary site of rhinovirus replication and responsible of initiating the host immune response to infection. Numerous studies have reported that the anti-viral innate immune response (including type I and type III interferon) in asthma is less effective or deficient leading to the conclusion that epithelial innate immunity is a key determinant of disease severity during a rhinovirus induced exacerbation. However, deficient rhinovirus-induced epithelial interferon production in asthma has not always been observed. We hypothesized that disparate in vitro airway epithelial infection models using high multiplicity of infection (MOI) and lacking genome-wide, time course analyses have obscured the role of epithelial innate anti-viral immunity in asthma and COPD. To address this, we developed a low MOI rhinovirus model of differentiated primary epithelial cells obtained from healthy, asthma and COPD donors. Using genome-wide gene expression following infection, we demonstrated that gene expression patterns are similar across patient groups, but that the kinetics of induction are delayed in cells obtained from asthma and COPD donors. Rhinovirus-induced innate immune responses were defined by interferons (type-I, II, and III), interferon response factors (IRF1, IRF3, and IRF7), TLR signaling and NF-κB and STAT1 activation. Induced gene expression was evident at 24 h and peaked at 48 h post-infection in cells from healthy subjects. In contrast, in cells from donors with asthma or COPD induction was maximal at or beyond 72–96 h post-infection. Thus, we propose that propensity for viral exacerbations of asthma and COPD relate to delayed (rather than deficient) expression of epithelial cell innate anti-viral immune genes which in turns leads to a delayed and ultimately more inflammatory host immune response.https://www.frontiersin.org/article/10.3389/fimmu.2020.00974/fullrhinovirusinterferon responseinnate immunityasthmachronic obstructive pulmonary disease (COPD)air-liquid interface (ALI) culture |