Asthmatic bronchial epithelial cells have a deficient innate immune response to infection with rhinovirus
Author(s)
Type
Journal 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-β
mRNA expression in asthmatic cultures and they produced
>2.5 times less interferon-β protein. In infected asthmatic cells, exogenous interferon-β
induced apoptosis and reduced
virus replication, demonstrating a causal link between deficient interferon-β, 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.
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-β
mRNA expression in asthmatic cultures and they produced
>2.5 times less interferon-β protein. In infected asthmatic cells, exogenous interferon-β
induced apoptosis and reduced
virus replication, demonstrating a causal link between deficient interferon-β, 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.
Date Issued
2005-03-21
Date Acceptance
2004-12-24
Citation
Journal of Experimental Medicine, 2005, 201 (6), pp.937-947
ISSN
1540-9538
Publisher
Rockefeller University Press
Start Page
937
End Page
947
Journal / Book Title
Journal of Experimental Medicine
Volume
201
Issue
6
Sponsor
British Medical Association
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000228062400013&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Grant Number
DPA/nj
Subjects
Science & Technology
Life Sciences & Biomedicine
Immunology
Medicine, Research & Experimental
Research & Experimental Medicine
IMMUNOLOGY
MEDICINE, RESEARCH & EXPERIMENTAL
INHALED CORTICOSTEROIDS
LOWER AIRWAYS
EXACERBATIONS
RECEPTOR
TRANSCRIPTION
INFLAMMATION
EXPRESSION
CHILDREN
VIRUSES
KINASE
Adult
Antiviral Agents
Apoptosis
Asthma
Bronchi
Caspase 3
Caspase 7
Caspases
Cells, Cultured
Epithelial Cells
Female
Gene Expression Regulation
Humans
Immunity, Innate
Interferon-beta
Male
Middle Aged
Picornaviridae Infections
RNA, Viral
Rhinovirus
Virus Replication
11 Medical And Health Sciences
Publication Status
Published