PUBLICATION
The chemokine receptor CXCR4 promotes granuloma formation by sustaining a mycobacteria-induced angiogenesis programme
- Authors
- Torraca, V., Tulotta, C., Snaar-Jagalska, B.E., Meijer, A.H.
- ID
- ZDB-PUB-170324-8
- Date
- 2017
- Source
- Scientific Reports 7: 45061 (Journal)
- Registered Authors
- Meijer, Annemarie H., Snaar-Jagalska, Ewa B., Torraca, Vincenzo
- Keywords
- Angiogenesis, Innate immunity, Mechanisms of disease, Tuberculosis
- MeSH Terms
-
- Animals
- Cell Movement/genetics
- Disease Models, Animal
- Gene Expression
- Genes, Reporter
- Granuloma/genetics
- Granuloma/metabolism*
- Granuloma/pathology*
- Inflammation/genetics
- Inflammation/metabolism
- Inflammation/pathology
- Macrophages/immunology
- Macrophages/metabolism
- Macrophages/microbiology
- Mutation
- Mycobacterium marinum*
- Neovascularization, Pathologic/etiology*
- Neovascularization, Pathologic/metabolism
- Receptors, CXCR4/genetics
- Receptors, CXCR4/metabolism*
- Signal Transduction
- Vascular Endothelial Growth Factor A/metabolism
- Zebrafish
- PubMed
- 28332618 Full text @ Sci. Rep.
Citation
Torraca, V., Tulotta, C., Snaar-Jagalska, B.E., Meijer, A.H. (2017) The chemokine receptor CXCR4 promotes granuloma formation by sustaining a mycobacteria-induced angiogenesis programme. Scientific Reports. 7:45061.
Abstract
CXC chemokine receptor 4 plays a critical role in chemotaxis and leukocyte differentiation. Furthermore, there is increasing evidence that links this receptor to angiogenesis. Using the well-established zebrafish-Mycobacterium marinum model for tuberculosis, angiogenesis was recently found to be important for the development of cellular aggregates called granulomas that contain the mycobacteria and are the hallmark of tuberculosis disease. Here, we found that initiation of the granuloma-associated proangiogenic programme requires CXCR4 signalling. The nascent granulomas in cxcr4b-deficient zebrafish embryos were poorly vascularised, which in turn also delayed bacterial growth. Suppressed infection expansion in cxcr4b mutants could not be attributed to an overall deficient recruitment of leukocytes or to different intramacrophage bacterial growth rate, as cxcr4b mutants displayed similar microbicidal capabilities against initial mycobacterial infection and the cellular composition of granulomatous lesions was similar to wildtype siblings. Expression of vegfaa was upregulated to a similar extent in cxcr4b mutants and wildtypes, suggesting that the granuloma vascularisation phenotype of cxcr4b mutants is independent of vascular endothelial growth factor.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping