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.
Highlights
Blood–brain barrier (BBB) integrity is necessary to protect the brain from injuries such as toxins and germs, as well as to help in maintaining central nervous system (CNS) homeostasis [1]
We decided to evaluate the capacity of B. abortus to activate human brain microvascular endothelial cells (HBMECs) in presence of platelets
HBMECs were co-cultured with platelets and infected with B. abortus (MOI of 100) for 24 h
Summary
Blood–brain barrier (BBB) integrity is necessary to protect the brain from injuries such as toxins and germs, as well as to help in maintaining central nervous system (CNS) homeostasis [1]. BBB activation and dysfunction contributes to several brain pathologies. Many factors are able to induce BBB. Pathogens 2020, 9, 708 dysfunction such as inflammatory mediators, matrix metalloproteinases, free radicals, and vascular endothelial growth factor, among others [2]. Bacteria of the genus Brucella produce several types of inflammatory disorders [3]. Neurobrucellosis is a neurodegenerative inflammatory disorder caused by invasion of the CNS by Brucella spp. and constitutes the most morbid pathology associated with this infection [4]. One of the most characteristic clinical signs of this disease is pleocytosis; i.e., the presence of leukocytes in the cerebrospinal fluid [4]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
