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
Citation
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):.
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
Probes
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping