Migrating Myeloid Cells Sense Temporal Dynamics of Chemoattractant Concentrations
Chemoattractant-mediated recruitment of hematopoietic cells to sites of pathogen growth or tissue damage is critical to host defense and organ homeostasis. Chemotaxis is typically considered to rely on spatial sensing, with cells following concentration gradients as long as these are present. Utiliz...
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Published in | Immunity (Cambridge, Mass.) Vol. 47; no. 5; pp. 862 - 874.e3 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Elsevier Inc
21.11.2017
Elsevier Limited |
Subjects | |
Online Access | Get full text |
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Summary: | Chemoattractant-mediated recruitment of hematopoietic cells to sites of pathogen growth or tissue damage is critical to host defense and organ homeostasis. Chemotaxis is typically considered to rely on spatial sensing, with cells following concentration gradients as long as these are present. Utilizing a microfluidic approach, we found that stable gradients of intermediate chemokines (CCL19 and CXCL12) failed to promote persistent directional migration of dendritic cells or neutrophils. Instead, rising chemokine concentrations were needed, implying that temporal sensing mechanisms controlled prolonged responses to these ligands. This behavior was found to depend on G-coupled receptor kinase-mediated negative regulation of receptor signaling and contrasted with responses to an end agonist chemoattractant (C5a), for which a stable gradient led to persistent migration. These findings identify temporal sensing as a key requirement for long-range myeloid cell migration to intermediate chemokines and provide insights into the mechanisms controlling immune cell motility in complex tissue environments.
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•Spatial cues initiate cell polarization in gradients of intermediate chemokines•Persistent migration to intermediate chemokines involves temporal sensing•G-coupled receptor kinase-dependent negative feedback prevents prolonged migration•Spatial cues are sufficient for persistent migration to end agonist attractants
Eukaryotic cells are known to perform directional migration along gradients of chemoattractants. Aronin et al. discovered that, for myeloid cells, certain (intermediate) chemokines need to have increasing absolute concentration over time to induce persistent migration, indicating that these cells are capable of sensing the temporal evolution of an immunological recruitment signal. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Equal contributions Lead Contact: Martin Meier-Schellersheim (mms@niaid.nih.gov) |
ISSN: | 1074-7613 1097-4180 |
DOI: | 10.1016/j.immuni.2017.10.020 |