CONICET | Buscador de Institutos y Recursos Humanos

Brucella abortus- activated microglia induces neuronal death throughcell to cell contact- and nitric oxide-dependet mechanism Ana Maria Rodriguez, María CruzMiraglia, Maria Victoria Delpino, Guillermo H Giambartolomei Instituto de Inmunología;Genética y Metabolismo (INIGEM) (CONICET-UBA) Abstract: Central nervous system invasion by bacteria of the genusBrucella results in an inflammatory disorder called neurobrucellosis. B.abortus infects microglia, eliciting the activation of this cells and theproduction of pro-inflammatory mediators. Previously, we demonstrated that B.abortus-ativated microglia induced neuronal death. The aim of this study was todetermine the putative mechanism involved in this phenomenon. Primary culturesof murine neurons were cultured alone or co- cultured with microglia fromprimary cultures infected or not with B. abortus. The viability of neuronsafter culture was determined by fluorescent microscopy. The role of nitricoxide was evaluated by using aminoguanidine, a selective inhibitor of iNOS. Asexpected, B. abortus-infected microglia induced neuronal death (p<0,005).Yet, in the presence of the aminoguanidine neuronal viability doesn?t differfrom non-infected microglia (p>0.05). To test whether directmicroglial?neuronal interaction was required for the execution of neuronaldeath, we added microglia to neuronal cultures either directly or physicallyseparated from neurons on transwell membrane inserts. In this case, we observedthat when the cells were separated by the transwell neuron viability was thesame than non-infected microglia in contact with neurons (p>0.05). Thus, B.abortus-activated microglia kills neurons by cell contact through anNO-depended mechanism. These results describe part of the mechanisms whereby B.abortus could induce neuronal death in neurobrucellosis.