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.
Highlights
The immune response relies on the migration of leukocytes and on their ability to stop in precise anatomical locations to fulfil their task
Using microfabricated channels that mimic the confined space of peripheral tissues, we have shown that the major histocompatibility complex (MHC) class II-associated invariant chain (Ii or CD74) regulates the motility of immature Dendritic cells (DCs) by imposing transient phases of slow locomotion[12]
As the main function of immature DCs is to sample their environment by engulfing large amounts of extracellular material, we investigated whether the pool of myosin IIA observed at the DC front plays a role in antigen uptake
Summary
The immune response relies on the migration of leukocytes and on their ability to stop in precise anatomical locations to fulfil their task. 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. In the mouse footpad and lung, DCs were shown to rather remain sessile and uptake luminal antigens through membrane projections that cross the epithelia[7,8,9,10] 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. We propose that this migration mode imposes on immature DCs a migratory behaviour that might facilitate their ability to detect scattered antigens, as suggested by a model based on intermittent search optimization
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