Ex vivo modeling of lung tissue resident antimicrobial responses

Pathogen interactions with the lungs are very dynamic processes. In biomedical research, it is paramount to model these processes in the laboratory as accurately as possible. Influenza A virus has been extensively studied in epithelial cell culture models, including advanced organoids and organ-on-a-chip systems. Here, we use ex vivo cultured precision cut lung slices (PCLS) and generate transcriptomic data to assess the global tissue resident host response to viral and bacterial challenges. Our data show (i) that murine PCLS faithfully reflect core responses to viral infection, while missing proinflammatory responses linked to infiltrating immune cells and (ii) that human PCLS show a highly diversified tissue resident immune response to viral infection due to previous exposures of the host to this pathogen. These responses are clearly distinct from antibacterial gene profiles. Our data advertise PCLS as a complex and realistic model to study tissue resident immune responses to microbes in a human system.