B. abortus-activated microglia induce neuronal death through primary phagocytosis.

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

Congreso; LXIV Reunión Anual de la Sociedad Argentina de Inmunología; 2016

Central nervous system invasion by bacteria of thegenus Brucella results in aninflammatory disorder called neurobrucellosis. B. abortus infects microglia, eliciting their activation andproduction of pro-inflammatory mediators. Evidence of neurological involvementoccurs to varying degrees in nervous systems of patients with neurobrucellosis.The aim of this work was to determine the putativemechanisms involved in this phenomenon. For this,we used murine primary cultures of neurons and microglia to demonstrate that,due to B. abortus infection, microglialprimary phagocytosis actively induces neuronal death, without inducing neuronalapoptosis. This phenomenon was due to microglia-TLR2 activation by Brucella lipoproteins. We demonstratedthat B. abortus-activated microgliasecrete nitric oxide (NO) and increase their phagocytic ability andproliferation (p<0.05). NO induced the exposure of eat-me signal on neurons(phosphatidylserine, PS). Blocking PS-binding protein milk fat globuleepidermal growth factor-8 (MFG-E8) interaction, or microglial vitronectinreceptor-MFG-E8 interaction was sufficient to prevent neuronal loss withoutinhibiting microglia activation (p<0.05). Hence, our results demonstrate anovel form of inflammatory neurodegeneration for a bacterial infection, whereinflammation cause exposure of eat-me signal on neurons, leading to their deaththrough primary phagocytosis. These results describepart of the mechanisms whereby B. abortus could induce neuronal death duringneurobrucellosis.