Differential interferon response of the cystic fibrosis bronchial epithelium to major and minor group rhinovirus infection

Abstract

Rhinoviruses (RVs) are the most prevalent respiratory viruses associated with acute pulmonary exacerbations of cystic fibrosis (CF), asthma, and chronic obstructive pulmonary disease (COPD). There is growing evidence that points to the involvement of the interferon (IFN) pathway in RV-associated morbidity in asthma and COPD. The mechanisms of acute RV-triggered exacerbations in CF are poorly understood. To assess the antiviral response of CF and healthy bronchial epithelial cells (BECs) to RV infection, we measured the levels of IFN-λ1, IFN-λ2/3, IFN-β, pattern recognition receptors (PRRs), and IFN-stimulated genes (ISGs) upon infection with major and minor group RVs and poly(IC) stimulation. The inflammatory response induced by RVs in CF and healthy BECs has also been evaluated. Major group RV infection of CF BECs resulted in a diminished IFN response at the level of IFNs (p=0.06), PRRs (p<0.05) and ISGs (p<0.01) in comparison to healthy BECs. However, IFN pathway induction of CF BECs upon minor group RV infection was preserved and similar to healthy BECs. Also, primary CF BECs had a constitutive inflammatory phenotype (p<0.001) and an increased inflammatory response to poly(IC) stimulation (p<0.001). Our in vitro data suggests that pathogen-specific interferon responses occur in CF lung disease.