01702nas a2200241   4500000000100000000000100001008004100002260000900043653001200052653001400064653002300078653003000101653002700131100001800158700002400176700002400200245010300224856006200327300001200389490000800401520103700409022001401446       2022                            d  c202210aex vivo10ainfection10aorganotypic models10aprecision-cut lung slices10arespiratory infections1 aFlávia Viana1 aCecilia M. O’Kane1 aGunnar N. Schroeder00aPrecision-cut lung slices: A powerful ex vivo model to investigate respiratory infectious diseases  uhttps://onlinelibrary.wiley.com/doi/abs/10.1111/mmi.14817  a578-5880 v1173 aRespiratory infections are a leading cause 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 recognized and employed as an 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.  a1365-2958