Traverses Brain Microvascular Endothelial Cells Using Infected Monocytes As a Trojan Horse

Neurobrucellosis is an inflammatory disease caused by the invasion of spp. to the central nervous system (CNS). The pathogenesis of the disease is not well characterized; however, for to gain access to the brain parenchyma, traversing of the blood-brain barrier (BBB) must take place. To understand the CNS determinants of the pathogenesis of , we have used the BBB model of human brain microvascular endothelial cells (HBMEC) to study the interactions between and brain endothelial cells. In this study, we showed that is able to adhere and invade HBMEC which was dependent on microtubules, microfilaments, endosome acidification and de novo protein synthesis. After infection, rapidly escapes the endosomal compartment of HBMEC and forms a replicative -containing vacuole that involves interactions with the endoplasmic reticulum. Despite the ability of to invade and replicate in HBMEC, the bacterium was unable by itself to traverse HBMEC, but could traverse polarized HBMEC monolayers within infected monocytes. Importantly, infected monocytes that traversed the HBMEC monolayer were a bacterial source for infection of glial cells. This is the first demonstration of the mechanism whereby is able to traverse the BBB and infect cells of the CNS. These results may have important implications in our understanding of the pathogenesis of neurobrucellosis.