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

RODRÍGUEZ, ANA MARÍA; TROTTA, ALDANA; MELNYCZAJKO, AGUSTINA P.; MIRAGLIA, M. CRUZ; KIM, KWANG SIK; DELPINO, M. VICTORIA; BARRIONUEVO, PAULA; GIAMBARTOLOMEI, GUILLERMO HERNÁN

Pathogens

mdpi

Lugar: Basel; Año: 2020 vol. 9

Central nervous system invasion by bacteria of the genus Brucella results in an inflammatorydisorder called neurobrucellosis. A common feature associated with this pathology is blood?brainbarrier (BBB) activation. However, the underlying mechanisms involved with such BBB activationremain unknown. The aim of this work was to investigate the role of Brucella abortus-stimulatedplatelets on human brain microvascular endothelial cell (HBMEC) activation. Platelets enhancedHBMEC activation in response to B. abortus infection. Furthermore, supernatants from B. abortusstimulatedplatelets 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 fromunstimulated platelets. Outer membrane protein 19, a B. abortus lipoprotein, recapitulated B. abortusmediated 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.