Protektiver Effekt von Interferon Typ I auf die Barrierefunktion des humanen Atemwegsepithels während einer Rhinovirus-Infektion

Human rhinovirus (HRV)-infections can be detected all year-round, particularly in September and are the most common cause of upper respiratory tract infections. In patients with chronic lung diseases, HRV-infections can trigger a significant worsening of symptoms, called exacerbations. Additionally, the barrier function of the airway epithelium can be impaired due to an infection with HRV and other respiratory viruses, which also increase the risk of bacterial co-infection. Currently, direct antiviral therapies and effective vaccinations are lacking against many respiratory viruses, including HRV. A possible approach for the development of new therapeutics could be the broad antiviral effect of interferons (IFNs) type I and type III. In vitro studies have shown that IFNs type I and III efficiently protect against viral infections. However, a deeper understanding of the protective effect of IFN during viral infections is required for a potential therapeutic application of these IFNs for respiratory infections. To date, it has not been shown if an IFN-pretreatment influences the virus-induced impairment of the barrier function of the airway epithelium. Therefore, the aim of this study was to investigate the effect of an IFN β1a pretreatment on the barrier function during HRV-infection. To this end, primary bronchial epithelial cells (pBECs) were used as model system and differentiated in air-liquid interface (ALI)-culture to form a pseudostratified epithelium. The cells where pretreated with IFN β1a and subsequently infected with HRV16 for 24 h to 72 h. The barrier function of untreated, HRV16-infected cells was decreased after 24 h, shown by decreased transepithelial resistance and increased permeability. After 48 h and 72 h the barrier function recovered but the tight junction-net was dissociated. IFN β1a-pretreated cells showed less HRV copy numbers, and neither a dissociation of tight junctions, nor decreased barrier function or cytotoxicity. Concluding, pretreatment with IFN β1a induced a protective effect not only on viral load but also on the barrier function. Additionally, an infection with HRV16 affected cilia, which were shortened or missing completely after viral infection. This effect aggravated over time, potentially reducing mucociliary clearance and therefore, the removal of pathogens, which in turn can facilitate bacterial penetration into the cell layer. However, pretreatment with IFN β1a also had protective effects regarding bacterial invasion. It could be shown that the translocation of Streptococcus pneumoniae into the cell layer of differentiated and IFN β1a-pretreated cells during an ongoing viral-bacterial co-infection was reduced. The mechanism by which HRV infections disrupt the airway epithelial barrier function is still unknown. Using the viral mimetic poly(I:C), we found no effect on the barrier function in differentiated ALI cultures. This result suggests that not the activation of antiviral signaling, but rather viral replication itself is causing the HRV-induced impairment of the airway epithelium. Taken together, this study shows the protective effect of IFN β1a pretreatment in differentiated primary bronchial epithelial cells during an infection with HRV16 and, additionally, the potential of IFN β1a to reduce bacterial invasion during viral-bacterial co-infection.