Respiratory viral infections can lead to dissociation of tight junctions (TJ) in the airway epithelium, which in turn can facilitate secondary bacterial infections. Type I interferons (IFNs) show protective effects against viral infection.

To investigate if IFN protects the epithelial barrier during viral infections, differentiated primary bronchial epithelial cells (pBECs) were pretreated with IFNβ and inoculated with human rhinovirus (HRV). After 24-72h, we quantified TJ areas (zonula occludens-1, ZO-1), transepithelial electric resistance (TEER), paracellular permeability, HRV copies and cytotoxity. To explore if IFN pretreatment affects secondary bacterial infections, pBECs were co-infected for 8h with Streptococcus pneumoniae (SP) after HRV-infection.

TJs in HRV-infected cells were significantly dissociated after 48 and 72h. A significant decrease in TEER and increased permeability was visible after 24h, as well as increasing cytotoxity in infected cells. In cells pre-treated with IFNβ, HRV copies were significantly lower than in untreated cells (mean+SD HRV 1.5x10^8 ± 2.9x10^8 vs HRV+IFNβ 1.7x10^5±1.8x10^5 copies/200ng RNA, p=0.013). Additionally, treated cells neither showed dissociation of TJs (mean+SD HRV 4939±810 µm² vs HRV+IFNβ 8526±1346 µm² ZO-1 area, p= 0.135), nor decreased TEER, increased permeability or cytotoxity. After co-infection with HRV and SP, penetration of bacteria into the cell layer was less profound in IFNβ treated cells (mean+SD -IFNβ 23.7 ± 10.9 vs +IFNβ 9.9 ± 3.5 % of cell layer depth, p=0.006).

Our findings show the protective effect of IFNβ pretreatment on tight junction of the airway epithelium during viral infection.