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

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.