Contribution of bronchial fibroblasts to the antiviral response in asthma.

Bedke, Nicole, Haitchi, Hans Michael, Xatzipsalti, Mara, Holgate, Stephen T. and Davies, Donna E. (2009) Contribution of bronchial fibroblasts to the antiviral response in asthma. Journal of Immunology, 182 (6), 3660-3667. (doi:10.4049/jimmunol.0802471).

Abstract

Human rhinoviruses (HRV) are a major cause of asthma exacerbations and hospitalization. Studies using primary cultures suggest that this may be due to impaired production of type I and type III IFNs by asthmatic bronchial epithelial cells. Although epithelial cells are the main target for HRV infection, HRV can be detected in the subepithelial layer of bronchial mucosa from infected subjects by in situ hybridization. Therefore, we postulated that submucosal fibroblasts are also involved in the innate antiviral response to HRV infection in asthma. We found that regardless of subject group, bronchial fibroblasts were highly susceptible to RV1b infection. IL-8 and IL-6 were rapidly induced by either HRV or UV-irradiated virus, suggesting that these responses did not require viral replication. In contrast, RANTES expression was dependent on viral replication. Regardless of disease status, fibroblasts did not respond to HRV infection with significant induction of IFN-beta, even though both groups responded to synthetic dsRNA with similar levels of IFN-beta expression. Exogenous IFN-beta was highly protective against viral replication. Our data suggest that fibroblasts respond to HRV with a vigorous proinflammatory response but minimal IFN-beta expression. Their susceptibility to infection may cause them to be a reservoir for HRV replication in the lower airways, especially in asthmatic subjects where there is reduced protection offered by epithelial-derived IFNs. Their ability to support viral replication coupled with their vigorous proinflammatory response following infection may contribute to asthma exacerbations.

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Contributors

Author: Hans Michael Haitchi

Author: Donna E. Davies

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