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Asthmatic bronchial epithelial cells have a deficient innate immune response to infection with rhinovirus.
J Exp Med 2005; 201(6):937-47JE

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.

Authors+Show Affiliations

The Brooke Laboratories, University of Southampton, Southampton SO16 6YD, UK. p.wark@soton.ac.ukNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15781584

Citation

Wark, Peter A B., et al. "Asthmatic Bronchial Epithelial Cells Have a Deficient Innate Immune Response to Infection With Rhinovirus." The Journal of Experimental Medicine, vol. 201, no. 6, 2005, pp. 937-47.
Wark PA, Johnston SL, Bucchieri F, et al. Asthmatic bronchial epithelial cells have a deficient innate immune response to infection with rhinovirus. J Exp Med. 2005;201(6):937-47.
Wark, P. A., Johnston, S. L., Bucchieri, F., Powell, R., Puddicombe, S., Laza-Stanca, V., ... Davies, D. E. (2005). Asthmatic bronchial epithelial cells have a deficient innate immune response to infection with rhinovirus. The Journal of Experimental Medicine, 201(6), pp. 937-47.
Wark PA, et al. Asthmatic Bronchial Epithelial Cells Have a Deficient Innate Immune Response to Infection With Rhinovirus. J Exp Med. 2005 Mar 21;201(6):937-47. PubMed PMID: 15781584.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Asthmatic bronchial epithelial cells have a deficient innate immune response to infection with rhinovirus. AU - Wark,Peter A B, AU - Johnston,Sebastian L, AU - Bucchieri,Fabio, AU - Powell,Robert, AU - Puddicombe,Sarah, AU - Laza-Stanca,Vasile, AU - Holgate,Stephen T, AU - Davies,Donna E, PY - 2005/3/23/pubmed PY - 2005/6/4/medline PY - 2005/3/23/entrez SP - 937 EP - 47 JF - The Journal of experimental medicine JO - J. Exp. Med. VL - 201 IS - 6 N2 - 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. SN - 0022-1007 UR - https://www.unboundmedicine.com/medline/citation/15781584/Asthmatic_bronchial_epithelial_cells_have_a_deficient_innate_immune_response_to_infection_with_rhinovirus_ L2 - http://jem.rupress.org/cgi/pmidlookup?view=long&pmid=15781584 DB - PRIME DP - Unbound Medicine ER -