Precision-cut lung slices: a powerful ex vivo model to investigate respiratory infectious diseases.

Respiratory infections are leading causes of mortality worldwide. Most of the research on the underlying disease mechanisms is based on cell culture, organoid or surrogate animal models. Although these provide important insights, they have limitations. Cell culture models fail to recapitulate cellular interactions in the lung and animal models often do not permit high-throughput analysis of drugs or pathogen isolates; hence, there is a need for improved, scalable models. Precision-cut lung slices (PCLS), small, uniform tissue slices generated from animal or human lungs are increasingly recognised and employed as ex vivo organotypic model. PCLS retain remarkable cellular complexity and the architecture of the lung, providing a platform to investigate respiratory pathogens in a near-native environment. Here we review the generation and features of PCLS, their use to investigate the pathogenesis of viral and bacterial pathogens and highlight their potential to advance respiratory infection research in the future.