Type III interferon(IFN-L) as a potential drug in SARS-CoV2 infection: Evaluation of antiviral and immune modulatory effects in a human in vitro model

discovery - Clinical courses of infections with severe acute respiratory syndrome coronavirus (SARS-CoV2) are characterized by viral replication in lung epithelial cells. Infection is accompanied with the activation of early innate immune reactions, in particular the induction of type I interferons (IFN-a/ß) and type III IFN (IFN-lambda). These IFNs are a group of cytokines that strongly restrict viral replication but have pronounced, albeit differential immune modulatory activities. Thereby, they not only control infections but they induce the secretion of inflammatory cytokines from infiltrating immune cells. In the severe courses of disease, these overshooting inflammatory reactions represent one of the most critical clinical phenotypes, which often cause the hardly controllable pathological consequences of the infection. Due to a restricted cell target spectrum of type III IFNs the proinflammatory site effects of type I IFNs are strongly reduced and might thus offer an opportunity for specific treatment. This project aims at elucidating the potential benefit of type III IFN in treating SARS-CoV2 infections. An advanced cell co-culture model based on human epithelial cells and human iPS cell-derived macrophages will be used to elucidate the antiviral properties as well as the immune modulatory consequences of IFN-lambda. Single cell RNA sequencing will determine viral replication, epithelial cell death vs tissue repair as well as the activation profile of macrophages, i.e. their pro-inflammatory vs. anti-inflammatory phenotype.