PUBLICATION

Disruption of Cxcr3 chemotactic signaling alters lysosomal function and renders macrophages more microbicidal

Authors
Sommer, F., Torraca, V., Xie, Y., In 't Veld, A.E., Willemse, J., Meijer, A.H.
ID
ZDB-PUB-210415-7
Date
2021
Source
Cell Reports   35: 109000 (Journal)
Registered Authors
Meijer, Annemarie H., Xie, Yufei
Keywords
chemotaxis, infection, inflammation, lysosome, macrophage, mycobacteria, vesicle, zebrafish
Datasets
GEO:GSE149942
MeSH Terms
  • Mycobacterium Infections/genetics*
  • Mycobacterium Infections/immunology
  • Mycobacterium Infections/microbiology
  • Macrophages/immunology*
  • Macrophages/microbiology
  • Macrophages/ultrastructure
  • Cell Tracking
  • Gene Expression Profiling
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/genetics*
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/immunology
  • Larva/immunology
  • Larva/microbiology
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/immunology
  • Signal Transduction/genetics
  • Signal Transduction/immunology*
  • Receptors, CXCR3/genetics*
  • Receptors, CXCR3/immunology
  • Lysosomes/immunology*
  • Lysosomes/metabolism
  • Lysosomes/microbiology
  • Lysosomes/ultrastructure
  • Genes, Reporter
  • Gene Expression Regulation
  • Sequence Analysis, RNA
  • Embryo, Nonmammalian
  • Mycobacterium marinum/immunology
  • Mycobacterium marinum/pathogenicity
  • Zebrafish/genetics*
  • Zebrafish/immunology
  • Zebrafish/microbiology
  • Luminescent Proteins/genetics
  • Luminescent Proteins/immunology
  • Mutation
  • Animals, Genetically Modified
  • Chemotaxis/genetics
  • Chemotaxis/immunology
  • Animals
  • Macrophage Activation
(all 39)
PubMed
33852860 Full text @ Cell Rep.
Abstract
Chemotaxis and lysosomal function are closely intertwined processes essential for the inflammatory response and clearance of intracellular bacteria. We used the zebrafish model to examine the link between chemotactic signaling and lysosome physiology in macrophages during mycobacterial infection and wound-induced inflammation in vivo. Macrophages from zebrafish larvae carrying a mutation in a chemokine receptor of the Cxcr3 family display upregulated expression of vesicle trafficking and lysosomal genes and possess enlarged lysosomes that enhance intracellular bacterial clearance. This increased microbicidal capacity is phenocopied by inhibiting the lysosomal transcription factor EC, while its overexpression counteracts the protective effect of chemokine receptor mutation. Tracking macrophage migration in zebrafish revealed that lysosomes of chemokine receptor mutants accumulate in the front half of cells, preventing macrophage polarization during chemotaxis and reaching sites of inflammation. Our work shows that chemotactic signaling affects the bactericidal properties and localization during chemotaxis, key aspects of the inflammatory response.
Genes / Markers
Figures
Figure Gallery (4 images)
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Expression
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
hu6044
    		Point Mutation
    ump2TgTransgenic Insertion
      1 - 2 of 2
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      Human Disease / Model
      No data available
      Sequence Targeting Reagents
      No data available
      Fish
      No data available
      Antibodies
      No data available
      Orthology
      No data available
      Engineered Foreign Genes
      Marker Marker Type Name
      mCherryEFGmCherry
      1 - 1 of 1
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      Mapping
      No data available
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      Citation
      Sommer, F., Torraca, V., Xie, Y., In 't Veld, A.E., Willemse, J., Meijer, A.H. (2021) Disruption of Cxcr3 chemotactic signaling alters lysosomal function and renders macrophages more microbicidal. Cell Reports. 35:109000.