PUBLICATION

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

Authors
Kam, J.Y., Cheng, T., Garland, D.C., Britton, W.J., Tobin, D.M., Oehlers, S.H.
ID
ZDB-PUB-220420-5
Date
2022
Source
Pathogens and disease   80(1): (Journal)
Registered Authors
Oehlers, Stefan, Tobin, David
Keywords
T cell, mycobacteria, neutrophil, vascular permeability, zebrafish
MeSH Terms
  • Animals
  • Capillary Permeability
  • Disease Models, Animal
  • Granuloma
  • Hypoxia
  • Mycobacterium*
  • Mycobacterium Infections, Nontuberculous*/microbiology
  • Mycobacterium marinum*/metabolism
  • Neutrophils
  • Zebrafish/microbiology
PubMed
35438161 Full text @ Pathog Dis
Abstract
Mycobacterial granuloma formation involves significant stromal remodeling including the growth of leaky, granuloma-associated vasculature. These permeable blood vessels aid mycobacterial growth, as anti-angiogenic or vascular normalizing therapies are beneficial host-directed therapies in pre-clinical 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 anti-angiogenic 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.
Genes / Markers
Figures
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Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping