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Inhibition of infection-induced vascular permeability modulates host leukocyte recruitment to Mycobacterium marinum granulomas in zebrafish.

Publication ,  Journal Article
Kam, JY; Cheng, T; Garland, DC; Britton, WJ; Tobin, DM; Oehlers, SH
Published in: Pathogens and disease
April 2022

Mycobacterial granuloma formation involves significant stromal remodeling including the growth of leaky, granuloma-associated vasculature. These permeable blood vessels aid mycobacterial growth, as antiangiogenic or vascular normalizing therapies are beneficial host-directed therapies in preclinical models of tuberculosis across host-mycobacterial pairings. Using the zebrafish-Mycobacterium marinum infection model, we demonstrate that vascular normalization by inhibition of vascular endothelial protein tyrosine phosphatase (VE-PTP) decreases granuloma hypoxia, the opposite effect of hypoxia-inducing antiangiogenic therapy. Inhibition of VE-PTP decreased neutrophil recruitment to granulomas in adult and larval zebrafish, and decreased the proportion of neutrophils that extravasated distal to granulomas. Furthermore, VE-PTP inhibition increased the accumulation of T cells at M. marinum granulomas. Our study provides evidence that, similar to the effect in solid tumors, vascular normalization during mycobacterial infection increases the T cell:neutrophil ratio in lesions which may be correlates of protective immunity.

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Published In

Pathogens and disease

DOI

EISSN

2049-632X

ISSN

2049-632X

Publication Date

April 2022

Volume

80

Issue

1

Start / End Page

ftac009

Related Subject Headings

  • Zebrafish
  • Neutrophils
  • Mycobacterium marinum
  • Mycobacterium Infections, Nontuberculous
  • Mycobacterium
  • Hypoxia
  • Granuloma
  • Disease Models, Animal
  • Capillary Permeability
  • Animals
 

Citation

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Kam, J. Y., Cheng, T., Garland, D. C., Britton, W. J., Tobin, D. M., & Oehlers, S. H. (2022). Inhibition of infection-induced vascular permeability modulates host leukocyte recruitment to Mycobacterium marinum granulomas in zebrafish. Pathogens and Disease, 80(1), ftac009. https://doi.org/10.1093/femspd/ftac009
Kam, Julia Y., Tina Cheng, Danielle C. Garland, Warwick J. Britton, David M. Tobin, and Stefan H. Oehlers. “Inhibition of infection-induced vascular permeability modulates host leukocyte recruitment to Mycobacterium marinum granulomas in zebrafish.Pathogens and Disease 80, no. 1 (April 2022): ftac009. https://doi.org/10.1093/femspd/ftac009.
Kam JY, Cheng T, Garland DC, Britton WJ, Tobin DM, Oehlers SH. Inhibition of infection-induced vascular permeability modulates host leukocyte recruitment to Mycobacterium marinum granulomas in zebrafish. Pathogens and disease. 2022 Apr;80(1):ftac009.
Kam, Julia Y., et al. “Inhibition of infection-induced vascular permeability modulates host leukocyte recruitment to Mycobacterium marinum granulomas in zebrafish.Pathogens and Disease, vol. 80, no. 1, Apr. 2022, p. ftac009. Epmc, doi:10.1093/femspd/ftac009.
Kam JY, Cheng T, Garland DC, Britton WJ, Tobin DM, Oehlers SH. Inhibition of infection-induced vascular permeability modulates host leukocyte recruitment to Mycobacterium marinum granulomas in zebrafish. Pathogens and disease. 2022 Apr;80(1):ftac009.
Journal cover image

Published In

Pathogens and disease

DOI

EISSN

2049-632X

ISSN

2049-632X

Publication Date

April 2022

Volume

80

Issue

1

Start / End Page

ftac009

Related Subject Headings

  • Zebrafish
  • Neutrophils
  • Mycobacterium marinum
  • Mycobacterium Infections, Nontuberculous
  • Mycobacterium
  • Hypoxia
  • Granuloma
  • Disease Models, Animal
  • Capillary Permeability
  • Animals