Brucella abortus traverses brain microvascular endothelial cells using infected monocytes as a Trojan horse

MIRAGLIA MC; RODRIGUEZ AM; 1.SCIAN R., BARRIONUEVO P., RODRIGUEZ A. M., ARRIOLA BENITEZ, P. C., GARCIA SAMARTINO C. , FOSSATI C. A., GIAMBARTOLOMEI G. H., DELPINO M. V.; RODRIGUEZ J; KIM KS; DENNIS V. A.; DELPINO MV; GIAMBARTOLOMEI GH

Frontiers in cellular and infection microbiology

Frontiers Media S.A.

Año: 2018

2235-2988

Neurobrucellosisis an inflammatory disease caused by the invasion of Brucella spp. to the central nervous system (CNS). The pathogenesisof the disease is not well characterized; however, for Brucella to gain access to the brain parenchyma, traversingof the blood-brain barrier (BBB) must take place. To understand the CNS determinantsof the pathogenesis of B. abortus, wehave used the in vitro BBB model ofhuman brain microvascular endothelial cells (HBMEC) to study the interactionsbetween B. abortus and brainendothelial cells. In this study, we showed that B. abortus is able to adhere and invade HBMEC which was dependenton microtubules, microfilaments, endosome acidification and de novo proteinsynthesis. After infection, B. abortus rapidly escapes the endosomalcompartment of HBMEC and forms a replicative Brucella-containing vacuole that involves interactions with theendoplasmic reticulum. Despite the ability of B. abortus to invade and replicate in HBMEC, thebacterium was unable by itself to traverse HBMEC, but could traverse polarizedHBMEC monolayers within infected monocytes. Importantly, infected monocytesthat traversed the HBMEC monolayer were a bacterial source for de novo infection of glial cells. Thisis the first demonstration of the mechanism whereby B. abortus is able to traverse the BBB and infect cells ofthe CNS. These results may have important implications in our understanding ofthe pathogenesis of neurobrucellosis.