Glia Cell-Elicited activation of brain microvascular in response to Brucella abortus infection requires ASC inflammasome-dependent IL-1beta production

MIRAGLIA, M. C.; COSTA FRANCO, MIRIAM M.; RODRIGUEZ, A. M.; BARRIONUEVO, P.; KWANG, S. KIM; DELPINO, M. V.; OLIVEIRA, SERGIO C.; GIAMBARTOLOMEI, G.H.

Buenos Aires

Congreso; IV LASID Meeting - LXIII Argentinean Society for Immunology Meeting - II French-Argentinean immunology meeting; 2015

LASID-SAI-FAIC

Blood-brain barrier activation is a common feature of human neurobrucellosis, but the underlying mechanisms are largely unknown. Recently, we have demonstrated that the activation of brain microvascular endothelial cells (HBMEC) by glial cells is mediated by Brucella-induced IL-1β through the activation of ASC and CASP-1. Since ASC is essential for the CASP-1 response to B. abortus in glial cells, a NLR should be involved in IL-1β production and the subsequent activation of HBMEC. To address whether NLRP3 and AIM2 are important for IL-1β secretion during infection of glial cells and activation of HBMEC, astrocytes and microglia from C57BL/6, NLRP3 and AIM2 KO mice were infected with B. abortus. HBMEC stimulation with culture supernatants (CS) from B. abortus-infected glial cells from WT mice induced 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 with CS from B. abortus-infected glial cells from NLRP3 and AIM2 KO mice (p