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

María C. Miraglia, Ana M. Rodriguez, Paula Barrionuevo, Julia Rodriguez, Kwang S. Kim, Vida A. Dennis, M. Victoria Delpino, Guillermo H. Giambartolomei

Research output: Contribution to journalArticle

Abstract

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 well characterized; however, for Brucella 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 B. abortus, we have used the in vitro BBB model of human brain microvascular endothelial cells (HBMEC) to study the interactions between B. abortus and brain endothelial cells. In this study, we showed that B. abortus is able to adhere and invade HBMEC which was dependent on microtubules, microfilaments, endosome acidification and de novo protein synthesis. After infection, B. abortus rapidly escapes the endosomal compartment of HBMEC and forms a replicative Brucella-containing vacuole that involves interactions with the endoplasmic reticulum. Despite the ability of B. abortus 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 de novo infection of glial cells. This is the first demonstration of the mechanism whereby B. abortus 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.

Original languageEnglish (US)
Article number200
JournalFrontiers in Cellular and Infection Microbiology
Volume8
Issue numberJUN
DOIs
StatePublished - Jun 14 2018

Keywords

  • Blood-brain barrier
  • Brucella abortus
  • Endothelial cells
  • Monocytes
  • Neurobrucellosis

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Microbiology (medical)
  • Infectious Diseases

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  • Cite this

    Miraglia, M. C., Rodriguez, A. M., Barrionuevo, P., Rodriguez, J., Kim, K. S., Dennis, V. A., Victoria Delpino, M., & Giambartolomei, G. H. (2018). Brucella abortus traverses brain microvascular endothelial cells using infected monocytes as a Trojan horse. Frontiers in Cellular and Infection Microbiology, 8(JUN), [200]. https://doi.org/10.3389/fcimb.2018.00200