ZFIN ID: ZDB-PUB-160809-12
Infection-induced vascular permeability aids mycobacterial growth
Oehlers, S.H., Cronan, M.R., Beerman, R.W., Johnson, M.G., Huang, J., Kontos, C.D., Stout, J.E., Tobin, D.M.
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* (all 20) expand
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.
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