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Brucella abortus-activated microglia induce neuronal death through primary phagocytosis.
Rodríguez, Ana M; Delpino, M Victoria; Miraglia, M Cruz; Costa Franco, Miriam M; Barrionuevo, Paula; Dennis, Vida A; Oliveira, Sergio C; Giambartolomei, Guillermo H.
Afiliação
  • Rodríguez AM; Instituto de Inmunología, Genética y Metabolismo (INIGEM), CONICET, Universidad de Buenos Aires, Buenos Aires, Argentina.
  • Delpino MV; Instituto de Inmunología, Genética y Metabolismo (INIGEM), CONICET, Universidad de Buenos Aires, Buenos Aires, Argentina.
  • Miraglia MC; Instituto de Inmunología, Genética y Metabolismo (INIGEM), CONICET, Universidad de Buenos Aires, Buenos Aires, Argentina.
  • Costa Franco MM; Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte-Minas Gerais, Brazil.
  • Barrionuevo P; Instituto de Medicina Experimental (CONICET-Academia Nacional de Medicina), Buenos Aires, Argentina.
  • Dennis VA; Center for Nano Biotechnology Research and Department of Biological Sciences, Alabama State University, Montgomery, AL.
  • Oliveira SC; Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte-Minas Gerais, Brazil.
  • Giambartolomei GH; Instituto de Inmunología, Genética y Metabolismo (INIGEM), CONICET, Universidad de Buenos Aires, Buenos Aires, Argentina.
Glia ; 65(7): 1137-1151, 2017 07.
Article em En | MEDLINE | ID: mdl-28398652
Inflammation has long been implicated as a contributor to pathogenesis in neurobrucellosis. Many of the associated neurocognitive symptoms of neurobrucellosis may be the result of neuronal dysfunction resulting from the inflammatory response induced by Brucella abortus 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 B. abortus infection. B. abortus was unable to infect or harm primary cultures of mouse neurons. However, when neurons were co-cultured with microglia and infected with B. abortus significant neuronal loss occurred. This phenomenon was dependent on TLR2 activation by Brucella lipoproteins. Neuronal death was not due to apoptosis, but it was dependent on the microglial release of nitric oxide (NO). B. abortus infection stimulated microglial proliferation, phagocytic activity and engulfment of neurons. NO secreted by B. abortus-activated microglia induced neuronal exposure of the "eat-me" signal phosphatidylserine (PS). Blocking of PS-binding to protein milk fat globule epidermal growth factor-8 (MFG-E8) or microglial vitronectin receptor-MFG-E8 interaction was sufficient to prevent neuronal loss by inhibiting microglial phagocytosis without affecting their activation. Taken together, our results indicate that B. abortus 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 B. abortus-activated microglia may explain, in part, the neurological deficits observed during neurobrucellosis.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fagocitose / Brucella abortus / Morte Celular / Microglia / Inflamação / Neurônios Limite: Animals Idioma: En Revista: Glia Assunto da revista: NEUROLOGIA Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Argentina País de publicação: Estados Unidos
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fagocitose / Brucella abortus / Morte Celular / Microglia / Inflamação / Neurônios Limite: Animals Idioma: En Revista: Glia Assunto da revista: NEUROLOGIA Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Argentina País de publicação: Estados Unidos