Faculty Opinions recommendation of Macropinocytosis overcomes directional bias in dendritic cells due to hydraulic resistance and facilitates space exploration.

SummaryThe 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 properties 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.

Download Full-text

Macropinocytosis Overcomes Directional Bias Due to Hydraulic Resistance to Enhance Space Exploration by Dendritic Cells

SSRN Electronic Journal ◽

10.2139/ssrn.3155703 ◽

2018 ◽

Cited By ~ 1

Author(s):

HHllne D. Moreau ◽

Carles Blanch-Mercader ◽

Rafaele Attia ◽

Zahraa Alraies ◽

Mathieu Maurin ◽

...

Keyword(s):

Dendritic Cells ◽

Hydraulic Resistance ◽

Space Exploration ◽

Directional Bias

Download Full-text

Macropinocytosis Overcomes Directional Bias in Dendritic Cells Due to Hydraulic Resistance and Facilitates Space Exploration

Developmental Cell ◽

10.1016/j.devcel.2019.03.024 ◽

2019 ◽

Vol 49 (2) ◽

pp. 171-188.e5 ◽

Cited By ~ 18

Author(s):

Hélène D. Moreau ◽

Carles Blanch-Mercader ◽

Rafaele Attia ◽

Mathieu Maurin ◽

Zahraa Alraies ◽

...

Keyword(s):

Dendritic Cells ◽

Hydraulic Resistance ◽

Space Exploration ◽

Directional Bias

Download Full-text

Faculty Opinions recommendation of Macropinocytosis overcomes directional bias in dendritic cells due to hydraulic resistance and facilitates space exploration.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.735530720.793559627 ◽

2019 ◽

Author(s):

Andrea McClatchey

Keyword(s):

Dendritic Cells ◽

Hydraulic Resistance ◽

Space Exploration ◽

Directional Bias

Download Full-text

Space exploration by dendritic cells requires maintenance of myosin II activity by IP 3 receptor 1

The EMBO Journal ◽

10.15252/embj.201489056 ◽

2015 ◽

Vol 34 (6) ◽

pp. 798-810 ◽

Cited By ~ 18

Author(s):

Paola Solanes ◽

Mélina L Heuzé ◽

Mathieu Maurin ◽

Marine Bretou ◽

Franziska Lautenschlaeger ◽

...

Keyword(s):

Dendritic Cells ◽

Space Exploration ◽

Myosin Ii

Download Full-text

Exhausted mature dendritic cells exhibit a slower and less persistent random motility but retain chemotaxis against CCL19

10.1101/2021.10.11.463881 ◽

2021 ◽

Author(s):

Yongjun Choi ◽

Vijaya Sunkara ◽

Yeojin Lee ◽

Yoon-Kyoung Cho

Keyword(s):

Dendritic Cells ◽

Space Exploration ◽

Cellular Migration ◽

Migration Behavior ◽

Cellular Motility ◽

Random Motility ◽

Peripheral Tissues ◽

Inflammatory Conditions ◽

Effective Immune Response ◽

Speed Fluctuation

Dendritic cells (DCs), which are immune sentinels in the peripheral tissues, play a number of roles, including patrolling for pathogens, internalising antigens, transporting antigens to the lymph nodes (LNs), interacting with T cells, and secreting cytokines. The well-coordinated migration of DCs under various immunological or inflammatory conditions is therefore essential to ensure an effective immune response. Upon maturation, DCs migrate faster and more persistently than immature DCs (iDCs), which is believed to facilitate CCR7-dependent chemotaxis. It has been reported that lipopolysaccharide-activated DCs produce IL-12 only transiently, and become resistant to further stimulation through exhaustion. However, little is known about the influence of DC exhaustion on cellular motility. Here, we studied the cellular migration of exhausted DCs in tissue-mimicked confined environments. We found that the speed of exhausted matured DCs (xmDCs) decreased significantly compared to active matured DCs (amDCs) and iDCs. In contrast, the speed fluctuation increased compared to that of amDCs and was similar to that of iDCs. In addition, the diffusivity of the xmDCs was significantly lower than that of the amDCs, which implies that DC exhaustion reduces the space exploration ability. Interestingly, CCR7-dependent chemotaxis against CCL19 in xmDCs was not considerably different from that observed in amDCs. Taken together, we report a unique intrinsic cell migration behavior of xmDCs, which exhibit a slower, less persistent, and less diffusive random motility, which results in the DCs remaining at the site of infection, although a well-preserved CCR7-dependent chemotactic motility is maintained.

Download Full-text

Chemotaxis overrides Barotaxis during Directional Decision-Making in Dictyostelium discoideum

10.1101/2020.01.14.904748 ◽

2020 ◽

Author(s):

Yuri Belotti ◽

David McGloin ◽

Cornelis J. Weijer

Keyword(s):

Decision Making ◽

Dendritic Cells ◽

Hydraulic Resistance ◽

Dictyostelium Discoideum ◽

Average Velocity ◽

Leading Edge ◽

Decision Threshold ◽

Chemical Gradient ◽

Critical Tension ◽

Micro Channels

AbstractNeutrophils and dendritic cells have, besides their well characterised chemotactic movement responses, been shown to be able to detect and respond to local differences in hydraulic resistance (barotaxis). Furthermore, for neutrophils, it has been suggested that barotaxis overrides chemotaxis. Here, we investigate whether Dictyostelium cells also respond to hydraulic resistance or primarily to chemical gradients using an asymmetric bifurcating micro-channel. This channel design allows us to decouple hydraulic and chemical stimuli, by providing a choice between moving up a chemical gradient or down a chemical gradient into a channel with 100 times lower hydraulic resistance. Under these conditions chemotaxis always overrides barotaxis. Cells confronted by a microchannel bifurcation are observed to often partially split their leading edge and to start moving into both channels. Cells in steeper cAMP gradients, that move faster, split more readily. The decision to retract the pseudopod moving away from the cAMP source is made when the average velocity of the pseudopod moving up the cAMP gradient is 20% higher than the average velocity of the pseudopod moving down the gradient. Surprisingly, this decision threshold is independent of the steepness of the cAMP gradient and speed of movement. It indicates that a critical force imbalance threshold underlies the repolarisation decision.Significance StatementWe investigate the directional ‘decision-making’ of Dictyostelium discoideum cells migrating within engineered micro-channels harbouring asymmetric bifurcations. Unlike neutrophils and immature dendritic cells, Dictyostelium cells strongly prioritise chemical over barotactic guidance cues. Cells in steeper cAMP gradients migrate at higher speeds, split their leading edges more readily when confronted with a bifurcation in the channel. The decision to retract a pseudopod pointing in an unfavourable direction occurs when a critical tension gradient between two competing pseudopods is surpassed. These experiments show that although barotaxis is not a major guidance cue, cellular mechanics plays a major role in leading edge dynamics, including front splitting and polarisation and retraction.

Download Full-text

Dendritic cells of the human epidermis: immuno-electron microscopic studies of la antigen reactivity

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100084090 ◽

1978 ◽

Vol 36 (2) ◽

pp. 644-645

Author(s):

G. Rowden ◽

M. G. Lewis ◽

T. M. Phillips

Keyword(s):

Dendritic Cells ◽

Langerhans Cells ◽

Cell Types ◽

Cell Type ◽

Electron Microscopic ◽

La Antigen ◽

Microscopic Studies ◽

A Cell ◽

C3 Receptors ◽

Antigen Reactivity

Langerhans cells of mammalian stratified squamous epithelial have proven to be an enigma since their discovery in 1868. These dendritic suprabasal cells have been considered as related to melanocytes either as effete cells, or as post divisional products. Although grafting experiments seemed to demonstrate the independence of the cell types, much confusion still exists. The presence in the epidermis of a cell type with morphological features seemingly shared by melanocytes and Langerhans cells has been especially troublesome. This so called "indeterminate", or " -dendritic cell" lacks both Langerhans cells granules and melanosomes, yet it is clearly not a keratinocyte. Suggestions have been made that it is related to either Langerhans cells or melanocyte. Recent studies have unequivocally demonstrated that Langerhans cells are independent cells with immune function. They display Fc and C3 receptors on their surface as well as la (immune region associated) antigens.

Download Full-text