The activation of human brain microvascular endothelial cells by brucella abortus-infected glial cells is mediated partially through TNF-alpha

MIRAGLIA, M. C.; RODRIGUEZ, A. M.; BARRIONUEVO P.; DELPINO, M.V.; GIAMBARTOLOMEI G.H.

Los cocos, Córdoba.

Congreso; LXI Reunión Anual de la Sociedad Argentina de Inmunología; 2013

Sociedad Argentina de Inmunología

B. abortus could interact with human brain microvascular endothelial cells (HBMEC) and gain access to the central nervous system and consequently elicit the inflammatory pathology called neurobrucellosis. We have recently demonstrated that although B. abortus can infect HBMEC, the indirect effect of glial cells infected with the bacterium, is more effective in activate the endothelium. Both, the TNF-á and IL-1â secreted by glial cells were reported to mediate HBMEC activation. Since we have demonstrated that these cytokines were secreted by astrocytes and microglia infected with B. abortus, we decided to investigate their role in B. abortus-mediated activation of HBMEC. To this end HBMEC were incubated with culture supernatants of B. abortus-infected astrocytes and microglia in the presence of an anti-TNF-a antibody or its isotype control. Activation of HBMEC was evaluated by cytokine secretion and expression of adhesion molecules. Supernatants from B. abortus-infected astrocytes and microglia induced the production of IL-6, IL-8 and MCP-1 and up-regulated the expression of CD54 (ICAM-1). Cytokine production and ICAM-1 expression was partially inhibited when supernatans were pre-incubated with anti-TNF-á antibody (p<0.001 vs. isotype control). The blocking of the TNF receptor on HBMECs with an anti-TNFRI antibody also partially inhibited (p<0.01 vs. isotype control) the above-mentioned parameters. These results indicated that activation of HBMEC by B. abortus-infected glial cells is mediated, at least in part, by TNF-á. The involvement of IL-1â on this phenomenon is currently under investigation.