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Article

Brucella abortus-Stimulated Platelets Activate Brain Microvascular Endothelial Cells Increasing Cell Transmigration through the Erk1/2 Pathway

1
Instituto de Inmunología, Genética y Metabolismo (INIGEM), CONICET, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires C1120AAD, Argentina
2
Instituto de Medicina Experimental (IMEX) (CONICET-Academia Nacional de Medicina), Buenos Aires C1425ASU, Argentina
3
Division of Pediatric Infectious Diseases, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
*
Author to whom correspondence should be addressed.
These authors have contributed equally to this work.
These authors share senior authorship.
§
Present address: Instituto de Virología, Centro de Investigación en Ciencias Veterinarias y Agronómicas, Instituto Nacional de Tecnología Agropecuaria (INTA), Hurlingham B1686, Argentina.
Pathogens 2020, 9(9), 708; https://doi.org/10.3390/pathogens9090708
Received: 27 July 2020 / Revised: 14 August 2020 / Accepted: 25 August 2020 / Published: 27 August 2020
(This article belongs to the Special Issue Host Immune Responses and Pathogenesis to Brucella spp. Infection)
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. View Full-Text
Keywords: Brucella abortus; neurobrucellosis; platelets; brain microvascular endothelial cells; endothelial cells Brucella abortus; neurobrucellosis; platelets; brain microvascular endothelial cells; endothelial cells
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MDPI and ACS Style

Rodríguez, A.M.; Trotta, A.; Melnyczajko, A.P.; Miraglia, M.C.; Kim, K.S.; Delpino, M.V.; Barrionuevo, P.; Giambartolomei, G.H. Brucella abortus-Stimulated Platelets Activate Brain Microvascular Endothelial Cells Increasing Cell Transmigration through the Erk1/2 Pathway. Pathogens 2020, 9, 708. https://doi.org/10.3390/pathogens9090708

AMA Style

Rodríguez AM, Trotta A, Melnyczajko AP, Miraglia MC, Kim KS, Delpino MV, Barrionuevo P, Giambartolomei GH. Brucella abortus-Stimulated Platelets Activate Brain Microvascular Endothelial Cells Increasing Cell Transmigration through the Erk1/2 Pathway. Pathogens. 2020; 9(9):708. https://doi.org/10.3390/pathogens9090708

Chicago/Turabian Style

Rodríguez, Ana M., Aldana Trotta, Agustina P. Melnyczajko, M. C. Miraglia, Kwang S. Kim, M. V. Delpino, Paula Barrionuevo, and Guillermo H. Giambartolomei 2020. "Brucella abortus-Stimulated Platelets Activate Brain Microvascular Endothelial Cells Increasing Cell Transmigration through the Erk1/2 Pathway" Pathogens 9, no. 9: 708. https://doi.org/10.3390/pathogens9090708

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