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

Abstract

The airway epithelium provides a crucial barrier against infection with respiratory pathogens. This barrier can be impaired following viral infection, paving the way for bacterial superinfections. Type I interferons (IFNs) are important antiviral mediators, and inhaled formulations of these glycoproteins are considered a potential approach for the treatment of respiratory viral infections. To investigate if type I IFNs can also protect against virus-induced epithelial barrier dysfunction, differentiated primary bronchial epithelial cells were pre-treated with IFN-β1a and subsequently infected with human rhinovirus (HRV) for 24 to 72h. Moreover, to functionally assess the effects of IFN-β1a pre-treatment on barrier integrity, we conducted co-infection experiments, in which cells were initially infected with HRV, and superinfected with Streptococcus pneumoniae 24 to 72 h later. In untreated cells, HRV infection significantly damaged ZO-1 positive tight junctions and cilia, and transiently increased permeability, whereas the barrier of cultures pre-treated with IFN-β1a remained intact. In co-infection experiments, bacteria were able to penetrate deeper into the cell layers of HRV-infected cultures than into those of uninfected cells. IFN-β1a pre-treatment abrogated virus-induced damage to the epithelial barrier. Taken together, these data demonstrate a beneficial effect of IFN-β in protecting epithelial barrier function in addition to its antiviral effects.