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Asthmatic bronchial epithelial cells have a deficient innate immune response to infection with rhinovirus

Asthmatic bronchial epithelial cells have a deficient innate immune response to infection with rhinovirus
Asthmatic bronchial epithelial cells have a deficient innate immune response to infection with rhinovirus
Rhinoviruses are the major trigger of acute asthma exacerbations and asthmatic subjects are more susceptible to these infections. To investigate the underlying mechanisms of this increased susceptibility, we examined virus replication and innate responses to rhinovirus (RV)-16 infection of primary bronchial epithelial cells from asthmatic and healthy control subjects.
Viral RNA expression and late virus release into supernatant was increased 50- and 7-fold, respectively in asthmatic cells compared with healthy controls. Virus infection induced late cell lysis in asthmatic cells but not in normal cells. Examination of the early cellular response to infection revealed impairment of virus induced caspase 3/7 activity and of apoptotic responses in the asthmatic cultures. Inhibition of apoptosis in normal cultures resulted in enhanced viral yield, comparable to that seen in infected asthmatic cultures. Examination of early innate immune responses revealed profound impairment of virus-induced interferon-ß mRNA expression in asthmatic cultures and they produced >2.5 times less interferon-ß protein. In infected asthmatic cells, exogenous interferon-ß induced apoptosis and reduced virus replication, demonstrating a causal link between deficient interferon-ß, impaired apoptosis and increased virus replication. These data suggest a novel use for type I interferons in the treatment or prevention of virus-induced asthma exacerbations.
0022-1007
937-947
Wark, Peter A.B.
df363708-b8e0-4f92-acd5-8bb7088e19d2
Johnston, Sebastian L.
90e0ef79-cfde-40e0-b301-90d3063ee036
Bucchieri, Fabio
d5c6c38a-8b02-4a37-afb0-c272033cb0d2
Powell, Robert
ab373473-8f49-4d7b-80e6-8d3234c5250c
Puddicombe, Sarah
124e2c4e-ab9a-46f3-855c-b54ed0b61cc4
Laza-Stanca, Vasile
b2753e13-40e9-41d5-8109-995410b75519
Holgate, Stephen T.
2e7c17a9-6796-436e-8772-1fe6d2ac5edc
Davies, Donna E.
7de8fdc7-3640-4e3a-aa91-d0e03f990c38
Wark, Peter A.B.
df363708-b8e0-4f92-acd5-8bb7088e19d2
Johnston, Sebastian L.
90e0ef79-cfde-40e0-b301-90d3063ee036
Bucchieri, Fabio
d5c6c38a-8b02-4a37-afb0-c272033cb0d2
Powell, Robert
ab373473-8f49-4d7b-80e6-8d3234c5250c
Puddicombe, Sarah
124e2c4e-ab9a-46f3-855c-b54ed0b61cc4
Laza-Stanca, Vasile
b2753e13-40e9-41d5-8109-995410b75519
Holgate, Stephen T.
2e7c17a9-6796-436e-8772-1fe6d2ac5edc
Davies, Donna E.
7de8fdc7-3640-4e3a-aa91-d0e03f990c38

Wark, Peter A.B., Johnston, Sebastian L., Bucchieri, Fabio, Powell, Robert, Puddicombe, Sarah, Laza-Stanca, Vasile, Holgate, Stephen T. and Davies, Donna E. (2005) Asthmatic bronchial epithelial cells have a deficient innate immune response to infection with rhinovirus. The Journal of Experimental Medicine, 201 (6), 937-947. (doi:10.1084/jem.20041901).

Record type: Article

Abstract

Rhinoviruses are the major trigger of acute asthma exacerbations and asthmatic subjects are more susceptible to these infections. To investigate the underlying mechanisms of this increased susceptibility, we examined virus replication and innate responses to rhinovirus (RV)-16 infection of primary bronchial epithelial cells from asthmatic and healthy control subjects.
Viral RNA expression and late virus release into supernatant was increased 50- and 7-fold, respectively in asthmatic cells compared with healthy controls. Virus infection induced late cell lysis in asthmatic cells but not in normal cells. Examination of the early cellular response to infection revealed impairment of virus induced caspase 3/7 activity and of apoptotic responses in the asthmatic cultures. Inhibition of apoptosis in normal cultures resulted in enhanced viral yield, comparable to that seen in infected asthmatic cultures. Examination of early innate immune responses revealed profound impairment of virus-induced interferon-ß mRNA expression in asthmatic cultures and they produced >2.5 times less interferon-ß protein. In infected asthmatic cells, exogenous interferon-ß induced apoptosis and reduced virus replication, demonstrating a causal link between deficient interferon-ß, impaired apoptosis and increased virus replication. These data suggest a novel use for type I interferons in the treatment or prevention of virus-induced asthma exacerbations.

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Published date: 2005

Identifiers

Local EPrints ID: 27474
URI: http://eprints.soton.ac.uk/id/eprint/27474
ISSN: 0022-1007
PURE UUID: 5f1db71a-db8e-4ac2-95be-615eb823d71c
ORCID for Donna E. Davies: ORCID iD orcid.org/0000-0002-5117-2991

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Date deposited: 25 Apr 2006
Last modified: 17 Dec 2019 02:04

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Contributors

Author: Peter A.B. Wark
Author: Sebastian L. Johnston
Author: Fabio Bucchieri
Author: Robert Powell
Author: Sarah Puddicombe
Author: Vasile Laza-Stanca
Author: Donna E. Davies ORCID iD

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