INIGEM   23989
INSTITUTO DE INMUNOLOGIA, GENETICA Y METABOLISMO
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
54. LXIII Reunión Anual de la Sociedad Argentina de Inmunología (SAI). 18-21 Noviembre de 2015.
Autor/es:
MARIA CRUZ MIRAGLIA; MIRIAM M. SILVA COSTA FRANCO,; ANA. M. RODRIGUEZ; PAULA BARRIONUEVO,; KIM KWANG S.; M. VICTORIA DELPINO,; SERGIO C. OLIVEIRA; GUILLERMO H. GIAMBARTOLOMEI
Reunión:
Congreso; 54. LXIII Reunión Anual de la Sociedad Argentina de Inmunología (SAI). 18-21 Noviembre de 2015.; 2015
Resumen:
Glia Cell-Elicited Activation of Brain Microvasculature in Response toBrucella abortus Infection Requires ASC Inflammasome-Dependent IL-1β Production Maria Cruz Miraglia1, Miriam M. SilvaCosta Franco2, Ana. M. Rodriguez1, Paula Barrionuevo3, Kim Kwang S.4, M. Victoria Delpino1, Sergio C. Oliveira2, Guillermo H.Giambartolomei1 1 Instituto de Inmunología, Genética y Metabolismo (CONICET/UBA). Hospitalde Clínicas ?José de San Martín?, Facultad de Medicina, Universidad de BuenosAires, Buenos Aires, Argentina 2 Departmentof Biochemistry and Immunology. Institute of Biological Sciences, FederalUniversity of Minas Gerais, Belo Horizonte-Minas Gerais, Brazil 3 Instituto de Medicina Experimental (CONICET-Academia Nacional deMedicina), Buenos Aires, Argentina 4 Divisionof Pediatric Infectious Diseases, Department of Pediatrics, Johns HopkinsUniversity School of Medicine, Baltimore, Maryland, USA Abstract: Blood-brain barrier activation is a common feature of humanneurobrucellosis, but the underlying mechanisms are largely unknown. Recently,we have demonstrated that the activation of brain microvascular endothelialcells (HBMEC) by glial cells is mediated by Brucella-induced IL-1β through the activation of ASC and CASP-1. Since ASCis essential for the CASP-1 response to B. abortus in glial cells, a NLR shouldbe involved in IL-1β production and thesubsequent activation of HBMEC. To address whether NLRP3 and AIM2 are importantfor IL-1β secretion during infection ofglial cells and activation of HBMEC, astrocytes and microglia from C57BL/6,NLRP3 and AIM2 KO mice were infected with B. abortus. HBMEC stimulation withculture supernatants (CS) from B. abortus-infected glial cells from WT miceinduced the secretion of IL-6, IL-8 and MCP-1 and the up-regulation of ICAM-1,while activation of HBMEC was abolished when these cells were stimulated withCS from B. abortus-infected glial cells from NLRP3 and AIM2 KO mice (p<0.001vs. WT). Transmigration of neutrophils and monocytes in an in vitro model ofbrain endothelium was also evaluated. Cellular transmigration occurred when themonolayer was stimulated with CS from WT glial cells, but it was not observedwhen HBMEC were stimulated with CS from NLRP3 and AIM2 KO cells (p<0.01 vs.WT). Experiments to ascertain whether inflammasome-dependent IL-1β production influences migration of cells into thebrain parenchyma are under investigation. These results demonstrate that ASCinflammasomes are critical for the glial activation of HBMEC by B. abortus.