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

Fabio Bucchieri, Sarah Puddicombe, Peter A.B. Wark, Stephen T. Holgate, Sebastian L. Johnston, Robert Powell, Donna E. Davies, Vasile Laza-Stanca

Risultato della ricerca: Articlepeer review

919 Citazioni (Scopus)

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-beta mRNA expression in asthmatic cultures and they produced >2.5 times less interferon-beta protein. In infected asthmatic cells, exogenous interferon-beta induced apoptosis and reduced virus replication, demonstrating a causal link between deficient interferon-beta, 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.
Lingua originaleEnglish
pagine (da-a)937-947
RivistaJournal of Experimental Medicine
Volume201(6)
Stato di pubblicazionePublished - 2005

All Science Journal Classification (ASJC) codes

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  • ???subjectarea.asjc.2400.2403???

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