Brucella abortus induces neuronal death through activation of microglia

RODRÍGUEZ A. M., MIRAGLIA M. C., COSTA FRANCO M. M. S., OLIVEIRA S. C., BARRIONUEVO P., JANCIC C., DELPINO M. V., GIAMBARTOLOMEI G. H

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

Central nervous system invasion by bacteria of the genus Brucella results in an inflammatory disorder called neurobrucellosis. B. abortus infects astrocytes and microglia, eliciting the production of pro-inflammatory cytokines which in turn induce glial apoptosis. The aim of this study was to determine the mechanisms of neuronal death induced by B. abortus. We evaluated the direct role of the bacterium on neurons and the effect that infected glial cell could have on them. For this, murine neurons were cultured alone or co-cultured with microglial cells (primary culture or the BV-2 cell line) in the presence or not of B. abortus. The viability of neurons was determined by microscopy and the secretion of cytokines by ELISA. Both, confocal microscopy using a GFP-B. abortus and determination of bacterial load demonstrated that B. abortus was unable to infect neurons or induce their death. Neurons were unable to secrete IL-6 y TNF-α in response to B. abortus (p>0,05 with respect to untreated cells). Yet, when neurons were co-cultured with infected microglia the number of viable neurons significantly decreased as a function of the number of microglia present in the culture (ratio neuron:microglia 1:20, 1:4, 1:2 y 1:1; p<0,05) and the amount of infecting bacteria (106, 107, 108 y 109 UFC/ml; p<0,05). This phenomenon was observed with primary microglia or BV-2 cells. Thus, although B. abortus was unable to directly induce neuronal death, the bacterium was able to kill neurons by activation of microglia, the macrophages of the central nervous system. These results describe part pf the mechanisms whereby B. abortus could induce neuronal death in neurobrucellosis.