Infection-Induced Vascular Permeability Aids Mycobacterial Growth.

Published

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 2017

Published In

Volume / Issue

  • 215 / 5

Start / End Page

  • 813 - 817

PubMed ID

  • 27496976

Pubmed Central ID

  • 27496976

Electronic International Standard Serial Number (EISSN)

  • 1537-6613

International Standard Serial Number (ISSN)

  • 0022-1899

Digital Object Identifier (DOI)

  • 10.1093/infdis/jiw355

Language

  • eng