Infection-Induced Vascular Permeability Aids Mycobacterial Growth.
Pathogenic mycobacteria trigger formation of organized granulomas. As granulomas mature, they induce angiogenesis and vascular permeability. Here, in a striking parallel to tumor pro-angiogenic signaling, we identify angiopoietin-2 (ANG-2) induction as an important component of vascular dysfunction during mycobacterial infection. Mycobacterial infection in humans and zebrafish results in robust induction of ANG-2 expression from macrophages and stromal cells. Using a small-molecule inhibitor closely related to one currently in clinical trials, we link ANG-2/TIE2 signaling to vascular permeability during mycobacterial infection. Targeting granuloma-induced vascular permeability via vascular endothelial-protein tyrosine phosphatase inhibition limits mycobacterial growth, suggesting a new strategy for host-directed therapies against tuberculosis.
Duke Scholars
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- Zebrafish
- Tuberculosis
- Signal Transduction
- Receptor, TIE-2
- Mycobacterium Infections
- Mycobacterium
- Microbiology
- Macrophages
- Larva
- Humans
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Zebrafish
- Tuberculosis
- Signal Transduction
- Receptor, TIE-2
- Mycobacterium Infections
- Mycobacterium
- Microbiology
- Macrophages
- Larva
- Humans