Resolving immune cells with patrolling behaviour by magnetic resonance time-lapse single cell tracking

Masthoff, Max; Freppon, Felix, Noah; Zondler, Lisa; Wilken, Enrica; Wachsmuth, Lydia; Niemann, Silke; Schwarz, Christian; Fredrich, Ina; Havlas, Asla; Block, Helena; Gerwing, Mirjam; Helfen, Anne; Heindel, Walter; Zarbock, Alexander; Wildgruber, Moritz, Faber, Cornelius

Abstract

Background Immune cells show distinct motion patterns that change upon inflammatory stimuli. Monocytes patrol the vasculature to screen for pathogens, thereby exerting an early task of innate immunity. Here, we aimed to non-invasively analyse single patrolling monocyte behaviour upon inflammatory stimuli. Methods We used time-lapse Magnetic Resonance Imaging (MRI) of the murine brain to dynamically track single patrolling monocytes within the circulation distant to the actual site of inflammation in different inflammatory conditions, ranging from a subcutaneous pellet model to severe peritonitis and bacteraemia. Findings Single patrolling immune cells with a velocity of <1 µm/s could be detected and followed dynamically using time-lapse MRI. We show, that due to local and systemic stimuli the slowly patrolling behaviour of monocytes is altered systemically and differs with type, duration and strength of the underlying stimulus. Interpretation Using time-lapse MRI, it is now possible to investigate the behaviour of single circulating monocytes over the course of the systemic immune response. Monocyte patrolling behaviour is altered systemically even before the onset of clinical symptoms distant to and depending on the underlying inflammatory stimulus.