Protective effect of interferon type I on barrier function of the human airway epithelium during rhinovirus infections in vitro

The airway epithelium with its tight junctions plays an important role as part of the mucosal immunity. Respiratory viral infections can lead to a dissociation of tight junction complexes. Type I Interferons (IFNs) activate the innate antiviral immunity and are proposed as inhaled antiviral treatments in several studies. To see if IFN additionally protects the barrier function during viral infections, differentiated primary bronchial epithelial cells were pretreated with IFNβ and subsequently inoculated with human rhinovirus (HRV) or poly(I:C) as a viral mimic. After 24h to 72h, tight junctions were quantified by immunofluorescence staining for zonula occludens-1 (ZO-1) and confocal microscopy. Additionally, transepithelial electric resistance (TEER), HRV copies and toxicity were determined. We observed a significant dissociation of tight junctions in HRV-infected cells after 48 and 72h, and a significant decrease in TEER after 24h. Increased cytopathic effect was also detected in cells with virus infection over time. The number of HRV copies was significantly lower in cells pretreated with IFNβ (mean±SD: HRV infection 3,88x10^8±6,52x10^8 vs IFNβ treated 4,52x10^5±3,37x10^5 copies/200ng RNA). Additionally, these cells neither showed dissociation of tight junctions (ZO-1 area, HRV infection 4863±541µm² vs IFNβ-treated 8317±1504µm²), nor decreased TEER or increased cytopathic effect. In contrast to HRV infection, poly(I:C) stimulation did not affect epithelial barrier integrity. Our findings suggest viral replication as a possible reason for barrier dysfunction and show the protective effect of IFN treatment on tight junction complexes of the airway epithelium.