 Cellular morphodynamics as quantifiers for functional states of resident tissue macrophages in vivoMiriam Schnitzerlein, Eric Greto, Anja Wegner, Anna Möller, Oliver Aust, Oumaima Ben Brahim, David B Blumenthal, Vasily Zaburdaev and Stefan Uderhardt PLOS Computational Biology, 2025, vol. 21, issue 5, 1-28 Abstract: Resident tissue macrophages (RTMs) are essential for tissue homeostasis. Their diverse functions, from monitoring interstitial fluids to clearing cellular debris, are accompanied by characteristic morphological changes that reflect their functional status. While current knowledge of macrophage behaviour comes primarily from in vitro studies, their dynamic behavior in vivo is fundamentally different, necessitating a more physiologically relevant approach to their understanding. In this study, we employed intravital imaging to generate dynamic data from peritoneal RTMs in mice under various conditions and developed a comprehensive image processing pipeline to quantify RTM morphodynamics over time, defining human-interpretable cell size and shape features. These features allowed for the quantitative and qualitative differentiation of cell populations in various functional states, including pro- and anti-inflammatory activation and endosomal dysfunction. The study revealed that under steady-state conditions, RTMs exhibit a wide range of morphodynamical phenotypes, constituting a naïve morphospace of behavioral motifs. Upon challenge, morphodynamic patterns changed uniformly at the population level but predominantly within the constraints of this naïve morphospace. Notably, aged animals displayed a markedly shifted naïve morphospace, indicating drastically different behavioral patterns compared to their young counterparts. The developed method also proved valuable in optimizing explanted tissue setups, bringing RTM behavior closer to the physiological native state. Our versatile approach thus provides novel insights into the dynamic behavior of bona fide macrophages in vivo, enabling the distinction between physiological and pathological cell states and the assessment of functional tissue age on a population level.Author summary: In this study, we combine state-of-the-art in vivo imaging with advanced computational analysis to reveal the dynamic behavior of peritoneal resident tissue macrophages (RTMs) in their natural environment. These sentinel cells, which are crucial for tissue homeostasis, constantly monitor their environment and, in the process, undergo dynamic morphological changes that have remained largely uninvestigated due to technical limitations. Using two-photon microscopy, we captured time-lapse images of RTMs in the peritoneal serosa under various experimental conditions. Our customized image processing pipeline allowed a comprehensive assessment of cell morphology and dynamics and provided unprecedented insights into the behavior of RTMs in vivo, enabling us to distinguish cell populations in different physiological and pathological states. Our work opens up new avenues for the dynamic in situ phenotyping of macrophage functionality in disease contexts without their extraction from tissues and provides a novel perspective on the behavior of RTMs in their natural microenvironment. This versatile tool promises to advance our understanding of tissue homeostasis and macrophage function in health and disease, with potential applications in both basic research and clinical settings. Date: 2025 Downloads: (external link) Related works: Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text Persistent link: https://EconPapers.repec.org/RePEc:plo:pcbi00:1011859 DOI: 10.1371/journal.pcbi.1011859 Access Statistics for this article More articles in PLOS Computational Biology from Public Library of Science |
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