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

ANA MARIA RODRIGUEZ; M. CRUZ MIRAGLIA; MIRIAM M. COSTA FRANCO; BARRIONUEVO PAULA; VIDA DENNIS; SERGIO C OLIVEIRA; MARIA VICTORIA DELPINO; GUILLERMO H. GIAMBARTOLOMEI

Congreso; 65. LXIV Reunión Anual de la Sociedad Argentina de Inmunología (SAI). 15-19 Noviembre 2016.; 2016

Central nervous system invasion by bacteria of the genus Brucellaresults in an inflammatory disorder called neurobrucellosis. B.abortus infects microglia, eliciting their activation and production ofpro-inflammatory mediators. Evidence of neurological involvementoccurs to varying degrees in nervous systems of patients withneurobrucellosis. The aim of this work was to determine the putativemechanisms involved in this phenomenon. For this, we usedmurine primary cultures of neurons and microglia to demonstratethat, due to B. abortus infection, microglial primary phagocytosisactively induces neuronal death, without inducing neuronal apoptosis.This phenomenon was due to microglia-TLR2 activation byBrucella lipoproteins. We demonstrated that B. abortus-activatedmicroglia secrete nitric oxide (NO) and increase their phagocyticability and proliferation (p<0.05). NO induced the exposure ofeat-me signal on neurons (phosphatidylserine, PS). BlockingPS-binding protein milk fat globule epidermal growth factor-8(MFG-E8) interaction, or microglial vitronectin receptor-MFG-E8interaction was sufficient to prevent neuronal loss without inhibitingmicroglia activation (p<0.05). Hence, our results demonstratea novel form of inflammatory neurodegeneration for a bacterialinfection, where inflammation cause exposure of eat-me signalon neurons, leading to their death through primary phagocytosis.These results describe part of the mechanisms whereby B. abortuscould induce neuronal death during neurobrucellosis.