Brucella abortus-stimulated platelets activate brain microvascular endothelial cells increasing cell transmigration through the ERK1/2 pathway

Ana María Rodríguez, Aldana Trotta, Agustina P. Melnyczajko, M. Cruz Miraglia, Kwang Sik Kim, M. Victoria Delpino, Paula Barrionuevo, Guillermo Hernán Giambartolomei

Research output: Contribution to journalArticlepeer-review

Abstract

Central nervous system invasion by bacteria of the genus Brucella results in an inflammatory disorder called neurobrucellosis. A common feature associated with this pathology is blood–brain barrier (BBB) activation. However, the underlying mechanisms involved with such BBB activation remain unknown. The aim of this work was to investigate the role of Brucella abortus-stimulated platelets on human brain microvascular endothelial cell (HBMEC) activation. Platelets enhanced HBMEC activation in response to B. abortus infection. Furthermore, supernatants from B. abortus-stimulated platelets also activated brain endothelial cells, inducing increased secretion of IL-6, IL-8, CCL-2 as well as ICAM-1 and CD40 upregulation on HBMEC compared with supernatants from unstimulated platelets. Outer membrane protein 19, a B. abortus lipoprotein, recapitulated B. abortus-mediated activation of HBMECs by platelets. In addition, supernatants from B. abortus-activated platelets promoted transendothelial migration of neutrophils and monocytes. Finally, using a pharmacological inhibitor, we demonstrated that the Erk1/2 pathway is involved in the endothelial activation induced by B. abortus-stimulated platelets and also in transendothelial migration of neutrophils. These results describe a mechanism whereby B. abortus-stimulated platelets induce endothelial cell activation, promoting neutrophils and monocytes to traverse the BBB probably contributing to the inflammatory pathology of neurobrucellosis.

Original languageEnglish (US)
Article number708
Pages (from-to)1-17
Number of pages17
JournalPathogens
Volume9
Issue number9
DOIs
StatePublished - Sep 2020

Keywords

  • Brain microvascular endothelial cells
  • Brucella abortus
  • Endothelial cells
  • Neurobrucellosis
  • Platelets

ASJC Scopus subject areas

  • Immunology and Allergy
  • Molecular Biology
  • Immunology and Microbiology(all)
  • Microbiology (medical)
  • Infectious Diseases

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