Migrating Myeloid Cells Sense Temporal Dynamics of Chemoattractant Concentrations

• Published in: Immunity (Cambridge, Mass.) Vol. 47; no. 5; pp. 862 - 874.e3
• Main Authors: Petrie Aronin, Caren E., Zhao, Yun M., Yoon, Justine S., Morgan, Nicole Y., Prüstel, Thorsten, Germain, Ronald N., Meier-Schellersheim, Martin
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 21.11.2017; Elsevier Limited
• Subjects: 3D migration chamber; adaptation; Animals; CCL19 protein; Cell Movement; Chemokine CCL19 - physiology; Chemokine CXCL12 - physiology; Chemokines; Chemotactic Factors - physiology; Chemotaxis; Concentration gradient; CXCL12 protein; Dendritic cells; Dendritic Cells - physiology; Detection; Eukaryotic chemotaxis; G-protein coupled receptor kinase; G-Protein-Coupled Receptor Kinase 3 - physiology; G-Protein-Coupled Receptor Kinases - physiology; Homeostasis; Leukocyte migration; Leukocytes (neutrophilic); Ligands; Mice; Mice, Inbred C57BL; Microfluidics; Myeloid cells; Myeloid Cells - physiology; Neutrophils; Signaling; spatial sensing; temporal sensing; adaptation; spatial sensing; Eukaryotic chemotaxis; 3D migration chamber; temporal sensing; G-protein coupled receptor kinase
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/j.immuni.2017.10.020

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. [Display omitted] •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.