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bioRxiv · 10.1101/2021.11.23.469781

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

Kam, J. Y.·Cheng, T.·Garland, D. C.·Britton, W. J. J.·Tobin, D. M.·Oehlers, S. H.
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Abstract

Mycobacterial granuloma formation involves significant stromal remodeling and 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. Here we demonstrate that vascular normalization through vascular endothelial-protein tyrosine phosphatase inhibition decreases granuloma hypoxia, the opposite effect of hypoxia-inducing anti-angiogenic therapy. Vascular normalization leads to increased T cell and decreased neutrophil recruitment to granulomas, correlates of a protective immune response against mycobacterial infection.

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Kam, J. Y., Cheng, T., Garland, D. C., Britton, W. J. J., Tobin, D. M., Oehlers, S. H.. 2021-11-23. Inhibition of infection-induced vascular permeability modulates host leukocyte recruitment to Mycobacterium marinum granulomas in zebrafish. https://doi.org/10.1101/2021.11.23.469781

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