Research ArticleDENDRITIC CELLS

Lysosome signaling controls the migration of dendritic cells

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Science Immunology  27 Oct 2017:
Vol. 2, Issue 16, eaak9573
DOI: 10.1126/sciimmunol.aak9573

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Lysosomal calcium powers dendritic cell migration

Activation of dendritic cells (DCs) by stimulus such as bacterial sensing promotes DC maturation. In contrast to random migratory patterns of immature DCs, mature DCs migrate in a continuous and directional manner. Here, Bretou et al. have examined the role of lysosomes in regulating migration of mature DCs. They report that release of lysosomal calcium connects DC activation with directional migration of DCs. Deletion of the lysosomal calcium channel transient receptor potential cation channel, mucolipin subfamily, member 1 (TRPML1) impaired directional DC migration and DC chemotaxis to lymph nodes. The authors propose the release of lysosomal calcium to be a key node that links stimulus sensing with DC migration.

Abstract

Dendritic cells (DCs) patrol their environment by linking antigen acquisition by macropinocytosis to cell locomotion. DC activation upon bacterial sensing inhibits macropinocytosis and increases DC migration, thus promoting the arrival of DCs to lymph nodes for antigen presentation to T cells. The signaling events that trigger such changes are not fully understood. We show that lysosome signaling plays a critical role in this process. Upon bacterial sensing, lysosomal calcium is released by the ionic channel TRPML1 (transient receptor potential cation channel, mucolipin subfamily, member 1), which activates the actin-based motor protein myosin II at the cell rear, promoting fast and directional migration. Lysosomal calcium further induces the activation of the transcription factor EB (TFEB), which translocates to the nucleus to maintain TRPML1 expression. We found that the TRPML1-TFEB axis results from the down-regulation of macropinocytosis after bacterial sensing by DCs. Lysosomal signaling therefore emerges as a hitherto unexpected link between macropinocytosis, actomyosin cytoskeleton organization, and DC migration.

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