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Many of the associated neurocognitive symptoms of neurobrucellosis may be the result of neuronal dysfunction resulting from the inflammatory response induced by <jats:italic>Brucella abortus<\/jats:italic> infection in the central nervous system. In this manuscript, we describe an immune mechanism for inflammatory activation of microglia that leads to neuronal death upon <jats:italic>B. abortus<\/jats:italic> infection. <jats:italic>B. abortus<\/jats:italic> was unable to infect or harm primary cultures of mouse neurons. However, when neurons were co\u2010cultured with microglia and infected with <jats:italic>B. abortus<\/jats:italic> significant neuronal loss occurred. This phenomenon was dependent on TLR2 activation by <jats:italic>Brucella<\/jats:italic> lipoproteins. Neuronal death was not due to apoptosis, but it was dependent on the microglial release of nitric oxide (NO). <jats:italic>B. abortus<\/jats:italic> infection stimulated microglial proliferation, phagocytic activity and engulfment of neurons. NO secreted by <jats:italic>B. abortus<\/jats:italic>\u2010activated microglia induced neuronal exposure of the \u201ceat\u2010me\u201d signal phosphatidylserine (PS). Blocking of PS\u2010binding to protein milk fat globule epidermal growth factor\u20108 (MFG\u2010E8) or microglial vitronectin receptor\u2010MFG\u2010E8 interaction was sufficient to prevent neuronal loss by inhibiting microglial phagocytosis without affecting their activation. Taken together, our results indicate that <jats:italic>B. abortus<\/jats:italic> is not directly toxic to neurons; rather, these cells become distressed and are killed by phagocytosis in the inflammatory surroundings generated by infected microglia. Neuronal loss induced by <jats:italic>B. abortus<\/jats:italic>\u2010activated microglia may explain, in part, the neurological deficits observed during neurobrucellosis.<\/jats:p>","DOI":"10.1002\/glia.23149","type":"journal-article","created":{"date-parts":[[2017,4,11]],"date-time":"2017-04-11T13:49:42Z","timestamp":1491918582000},"page":"1137-1151","source":"Crossref","is-referenced-by-count":44,"title":["<i>Brucella abortus<\/i>\u2010activated microglia induce neuronal death through primary phagocytosis"],"prefix":"10.1002","volume":"65","author":[{"given":"Ana M.","family":"Rodr\u00edguez","sequence":"first","affiliation":[{"name":"Instituto de Inmunolog\u00eda, Gen\u00e9tica y Metabolismo (INIGEM), CONICET, Universidad de Buenos Aires Buenos Aires Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. 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