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

Central nervous system invasion by bacteria of the genusBrucellaresults 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 ofBrucella abortus-stimulated platelets on human brain microvascular endothelial cell (HBMEC) activation. Platelets enhanced HBMEC activation in response toB. abortusinfection. Furthermore, supernatants fromB. 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, aB. abortuslipoprotein, recapitulatedB. abortus-mediated activation of HBMECs by platelets. In addition, supernatants fromB. 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 byB. abortus-stimulated platelets and also in transendothelial migration of neutrophils. These results describe a mechanism wherebyB. abortus-stimulated platelets induce endothelial cell activation, promoting neutrophils and monocytes to traverse the BBB probably contributing to the inflammatory pathology of neurobrucellosis.