Infection-Induced Vascular Permeability Aids Mycobacterial Growth.
Journal Article (Journal Article)
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.
Full Text
Duke Authors
Cited Authors
- Oehlers, SH; Cronan, MR; Beerman, RW; Johnson, MG; Huang, J; Kontos, CD; Stout, JE; Tobin, DM
Published Date
- March 1, 2017
Published In
Volume / Issue
- 215 / 5
Start / End Page
- 813 - 817
PubMed ID
- 27496976
Pubmed Central ID
- PMC5853473
Electronic International Standard Serial Number (EISSN)
- 1537-6613
Digital Object Identifier (DOI)
- 10.1093/infdis/jiw355
Language
- eng
Conference Location
- United States