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In the fast phase (ii; blue cell) of mean duration (b) Antigen mean search time between antigen locations

Posted on February 10, 2022 by president2010

In the fast phase (ii; blue cell) of mean duration (b) Antigen mean search time between antigen locations. blue for eye tracking. The fluorescent content of vesicles becomes brighter upon exocytosis. Images were acquired on a spinning disk microscope every 30 s MK-0359 (60X objective). ncomms8526-s4.mov (2.7M) GUID:?CB6746F6-EDE0-4BF7-BB21-E14A1E899C93 MK-0359 Supplementary Movie 4 High-resolution dynamics of myosin IIA-GFP at the cell front in and immature DCs migrating in micro-channels. Images were acquired on a spinning disk microscope every 10 s (60X objective, middle plane). ncomms8526-s5.mov (6.9M) GUID:?B3A3A0CB-F9E5-43E6-B8FA-AA412A78AD3D Supplementary Movie 5 Accumulation of AF488-Ovalbumin (OVA) in CypHer5E-positive endolysosomal compartments in immature and DCs migrating in micro-channels. Images were acquired on an epifluorescence microscope every min (20X objective). ncomms8526-s6.mov (6.3M) GUID:?0000692E-4108-44EE-93C6-36EA7A1591B7 Abstract The immune response relies on the migration of leukocytes and on their ability to stop in precise anatomical locations to fulfil their task. How leukocyte migration and function are coordinated is unknown. Here we show that in immature dendritic cells, which patrol their environment by engulfing extracellular material, cell migration and antigen capture are antagonistic. This antagonism results from transient enrichment of myosin IIA at the cell front, which disrupts the back-to-front gradient of the motor protein, slowing down locomotion but promoting antigen capture. We further highlight that myosin IIA enrichment at the cell front requires the MHC class II-associated invariant chain (Ii). Thus, by controlling myosin IIA localization, Ii imposes on dendritic cells an intermittent antigen capture behaviour that might facilitate environment patrolling. We propose that the requirement for myosin II in both cell migration and specific cell functions may provide a general mechanism for their coordination in time and space. Dendritic cells (DCs) are in charge of capturing antigens in peripheral tissues, transporting them to lymph nodes and presenting them on major histocompatibility complex (MHC) molecules to T lymphocytes. This process referred to as antigen presentation leads to T-cell activation and is essential for the onset of the adaptive immune response. In tissues, immature DCs capture antigens mainly by phagocytosis and macropinocytosis1. This actin-dependent mode of internalization allows the nonspecific uptake of large amounts of extracellular fluid and, in DCs, relies on the small GTPases Cdc42 and Rac1 (refs 2, 3). Taken-up antigens are delivered to endolysosomes, where they are degraded into peptides to be loaded on MHC class II molecules4. How immature DCs uptake antigens to exert their patrolling function has recently started to be documented. Two-photon imaging experiments suggest that in certain tissues, such as the mouse ear and gut, DCs randomly migrate to scan the environment5,6. In contrast, in the mouse footpad and lung, DCs were shown to rather remain sessile and uptake luminal antigens through membrane projections that cross the epithelia7,8,9,10. Whether these different DC behaviours rely on cell-intrinsic mechanisms that allow the coordination between their antigen capture function and their migratory capacity remains unknown. The mechanisms that regulate DC migration are not fully understood. An essential role was attributed to the actin-based motor protein myosin II. Its activity is required both and for migrating DCs to reach their maximal speed in three-dimensional (3D) environments11,13. Integrin-dependent adhesion was found to be dispensable to this process11. Using microfabricated Nes channels that mimic the confined space of peripheral tissues, we have shown that the MHC class II-associated invariant chain (Ii or CD74) regulates the motility of immature DCs by imposing transient phases of slow locomotion12. In addition, myosin IIA and Ii were found to physically interact in both DCs and B cells12,14. However, neither the mechanism by which Ii reduces DC locomotion nor the impact of such regulation on the antigen capture function of DCs has been highlighted so far. Here we show that antigen capture and DC migration both require myosin IIA. Efficient antigen uptake by macropinocytosis is associated with periodic enrichments of Myosin IIA MK-0359 at the DC front. These enrichments disrupt the back-to-front myosin IIA gradient responsible for fast locomotion and therefore slow down.

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