Ana Maria Lennon Duménil - Dendritic Cell migration: from microfluidics to in vivo imaging
Channel: Institut des Hautes Études Scientifiques (IHÉS)
Date: 2018-03-26

The migration of immune cells is guided by specific chemical signals, such as chemokine gradients. Their trajectories can also be diverted by physical cues and obstacles imposed by the cellular environment, such as topography, rigidity, adhesion, or hydraulic 
resistance. On the example of hydraulic resistance, it was shown that neutrophil preferentially follow paths of least resistance, a phenomenon referred to as  barotaxis.  We  here  combined  quantitative  imaging  and  physical  modeling  to  show  that  barotaxis results from a force imbalance at the scale of the cell, which is amplified by the acto-myosin intrinsic polarization  capacity.  Strikingly,  we  found  that  macropinocytosis  specifically  confers  to  immature dendritic cells a unique capacity to overcome this physical bias by facilitating external fluid transport across the cell, thereby enhancing their space exploration capacity in vivo and promoting their tissue-patrolling  function.  Conversely,  mature  dendritic  cells,  which  down-regulate  macropinocytosis,  were found to be sensitive to hydraulic resistance. Theoretical modeling suggested that barotaxis, which helps them  avoid  dead-ends,  may  accelerate  their  migration  to  lymph  nodes,  where  they  initiate  adaptive 
immune responses. We conclude that the physical propert
ies of the microenvironment of moving cells can  introduce  biases  in  their  migratory  behaviors  but  that  specific  active mechanisms  such  as macropinocytosis have emerged to diminish the influence of these biases, allowing motile cells to reach their final destination and efficiently fulfill their functions