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.
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
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping