Brucella abortus Traverses Brain Microvascular Endothelial Cells Using Infected Monocytes as a Trojan Horse

MARIA CRUZ MIRAGLIA*EQUALLY CONTRIBUTION; ANA MARÍA RODRIGUEZ*EQUALLY CONTRIBUTION; BARRIONUEVO PAULA; JULIA RODRIGUEZ; KWANG S. KIM; VIDA A. DENNIS; M. VICTORIA DELPINO; GUILLERMO H. GIAMBARTOLOMEI

Frontiers in Cellular and Infection Microbiology

Frontiers

Año: 2018

2235-2988

Neurobrucellosis is an inflammatory disease caused by the invasion of Brucella spp.to the central nervous system (CNS). The pathogenesis of the disease is not wellcharacterized; 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, we have used the in vitro BBB model of human brainmicrovascular endothelial cells (HBMEC) to study the interactions between B. abortusand brain endothelial cells. In this study, we showed that B. abortus is able to adhereand invade HBMEC which was dependent on microtubules, microfilaments, endosomeacidification and de novo protein synthesis. After infection, B. abortus rapidly escapes theendosomal compartment of HBMEC and forms a replicative Brucella-containing vacuolethat involves interactions with the endoplasmic reticulum. Despite the ability of B. abortusto invade and replicate in HBMEC, the bacteriumwas 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 forde novo infection of glial cells. This is the first demonstration of the mechanism wherebyB. abortus is able to traverse the BBB and infect cells of the CNS. These resultsmay haveimportant implications in our understanding of the pathogenesis of neurobrucellosis.