• Marjolaine Vareille, Elisabeth Kieninger, Marco P Alves, Brigitte S Kopf, Alexander Möller, Thomas Geiser, Sebastian L Johnston, Michael R Edwards, and Nicolas Regamey.
• Department of Clinical Research, University of Bern, Bern, Switzerland.
• Thorax. 2012 Jun 1;67(6):517-25.

BackgroundRhinoviruses are important triggers of pulmonary exacerbations and possible contributors to long-term respiratory morbidity in cystic fibrosis (CF), but mechanisms leading to rhinovirus-induced CF exacerbations are poorly understood. It is hypothesised that there is a deficient innate immune response of the airway epithelium towards rhinovirus infection in CF.MethodsEarly innate immune responses towards rhinoviruses (RV-16, major-type and RV-1B, minor-type) in CF and non-CF bronchial epithelial cell lines and primary nasal and bronchial epithelial cells from patients with CF (n=13) and healthy controls (n=24) were studied.ResultsRhinovirus RNA expression and virus release into supernatants was increased more than tenfold in CF cells compared with controls. CF cells expressed up to 1000 times less interferon (IFN) type I (β) and type III (λ) mRNA and produced less than half of IFN-β and IFN-λ protein compared with controls. In contrast, interleukin 8 production was not impaired, indicating a selective deficiency in the innate antiviral defence system. Deficient IFN production was paralleled by lower expression of IFN-stimulated genes including myxovirus resistance A, 2',5'-oligoadenylate synthetase, viperin and nitric oxide synthase 2. Addition of exogenous type I and III IFNs, particularly IFN-β, restored antiviral pathways and virus control in CF cells, underscoring the crucial role of these molecules.ConclusionsThis study describes a novel mechanism to explain the increased susceptibility of patients with CF to rhinovirus infections. A profound impairment of the antiviral early innate response in CF airway epithelial cells was identified, suggesting a potential use of IFNs in the treatment of rhinovirus-induced CF exacerbations.

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