PUBLICATION
Infection-induced vascular permeability aids mycobacterial growth
- Authors
- Oehlers, S.H., Cronan, M.R., Beerman, R.W., Johnson, M.G., Huang, J., Kontos, C.D., Stout, J.E., Tobin, D.M.
- ID
- ZDB-PUB-160809-12
- Date
- 2017
- Source
- The Journal of infectious diseases 215(5): 813-817 (Journal)
- Registered Authors
- Beerman, Rebecca, Cronan, Mark, Oehlers, Stefan, Tobin, David
- Keywords
- Mycobacterium tuberculosis, granuloma, vascular permeability, angiopoietin, TIE2, VE-PTP, zebrafish
- MeSH Terms
-
- Angiopoietin-2/genetics
- Angiopoietin-2/metabolism*
- Animals
- Animals, Genetically Modified
- Capillary Permeability*
- Disease Models, Animal
- Gene Expression Regulation
- Granuloma/microbiology
- Host-Pathogen Interactions
- Humans
- Larva
- Macrophages/drug effects
- Macrophages/microbiology
- Mycobacterium/drug effects
- Mycobacterium/growth & development*
- Mycobacterium Infections/pathology*
- Receptor, TIE-2/metabolism
- Signal Transduction
- Tuberculosis/microbiology
- Zebrafish
- PubMed
- 27496976 Full text @ J. Infect. Dis.
Citation
Oehlers, S.H., Cronan, M.R., Beerman, R.W., Johnson, M.G., Huang, J., Kontos, C.D., Stout, J.E., Tobin, D.M. (2017) Infection-induced vascular permeability aids mycobacterial growth. The Journal of infectious diseases. 215(5):813-817.
Abstract
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 VE-PTP inhibition limits mycobacterial growth, suggesting a new strategy for host-directed therapies against tuberculosis.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping