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
-
- Animals
- Animals, Genetically Modified
- Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/genetics*
- Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/immunology
- Cell Tracking
- Chemotaxis/genetics
- Chemotaxis/immunology
- Embryo, Nonmammalian
- Gene Expression Profiling
- Gene Expression Regulation
- Genes, Reporter
- Larva/immunology
- Larva/microbiology
- Luminescent Proteins/genetics
- Luminescent Proteins/immunology
- Lysosomes/immunology*
- Lysosomes/metabolism
- Lysosomes/microbiology
- Lysosomes/ultrastructure
- Macrophage Activation
- Macrophages/immunology*
- Macrophages/microbiology
- Macrophages/ultrastructure
- Mutation
- Mycobacterium Infections/genetics*
- Mycobacterium Infections/immunology
- Mycobacterium Infections/microbiology
- Mycobacterium marinum/immunology
- Mycobacterium marinum/pathogenicity
- Receptors, CXCR3/genetics*
- Receptors, CXCR3/immunology
- Sequence Analysis, RNA
- Signal Transduction/genetics
- Signal Transduction/immunology*
- Zebrafish/genetics*
- Zebrafish/immunology
- Zebrafish/microbiology
- Zebrafish Proteins/genetics*
- Zebrafish Proteins/immunology
- PubMed
- 33852860 Full text @ Cell Rep.
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.
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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping