Role of extracellular mycobacteria in blood-retinal barrier invasion in a zebrafish model of ocular TB

Intraocular inflammation following mycobacterial dissemination to the eye is common in tuberculosis (TB)-endemic countries. However, the early host-pathogen interactions during ocular dissemination are unknown. In this study, we investigate the early events during mycobacterial invasion of the blood-retinal barriers (BRB) with fluorescent tagged Mycobacterium marinum ( Mm ), host macrophages and retinal vasculature in a zebrafish model of ocular TB. We found that Mm invaded the vascular endothelium either in extracellular or intracellular (inside phagocytes) state, typically 3-4 days post-injection (dpi). Extracellular Mm are phagocytosed in the retinal tissue, and progress to form a compact granuloma around 6 dpi. Intracellular Mm crossing the BRB are likely to be less virulent, and either persist inside solitary macrophages (most cases), or progress to loosely arranged granuloma (rare). The early interactions between mycobacteria and host immune cells can thus determine the course of disease during mycobacterial dissemination to the eye.