{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T13:18:55Z","timestamp":1789996735299,"version":"4.0.1"},"reference-count":63,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2016,5,1]],"date-time":"2016-05-01T00:00:00Z","timestamp":1462060800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Blood\u2013brain barrier activation and\/or dysfunction are a common feature of human neurobrucellosis, but the underlying pathogenic mechanisms are largely unknown. In this article, we describe an immune mechanism for inflammatory activation of human brain microvascular endothelial cells (HBMEC) in response to infection with Brucella abortus. Infection of HBMEC with B. abortus induced the secretion of IL-6, IL-8, and MCP-1, and the upregulation of CD54 (ICAM-1), consistent with a state of activation. Culture supernatants (CS) from glial cells (astrocytes and microglia) infected with B. abortus also induced activation of HBMEC, but to a greater extent. Although B. abortus\u2013infected glial cells secreted IL-1\u03b2 and TNF-\u03b1, activation of HBMEC was dependent on IL-1\u03b2 because CS from B. abortus\u2013infected astrocytes and microglia deficient in caspase-1 and apoptosis-associated speck-like protein containing a CARD failed to induce HBMEC activation. Consistently, treatment of CS with neutralizing anti\u2013IL-1\u03b2 inhibited HBMEC activation. Both absent in melanoma 2 and Nod-like receptor containing a pyrin domain 3 are partially required for caspase-1 activation and IL-1\u03b2 secretion, suggesting that multiple apoptosis-associated speck-like protein containing CARD\u2013dependent inflammasomes contribute to IL-1\u03b2\u2013induced activation of the brain microvasculature. Inflammasome-mediated IL-1\u03b2 secretion in glial cells depends on TLR2 and MyD88 adapter-like\/TIRAP. Finally, neutrophil and monocyte migration across HBMEC monolayers was increased by CS from Brucella-infected glial cells in an IL-1\u03b2\u2013dependent fashion, and the infiltration of neutrophils into the brain parenchyma upon intracranial injection of B. abortus was diminished in the absence of Nod-like receptor containing a pyrin domain 3 and absent in melanoma 2. Our results indicate that innate immunity of the CNS set in motion by B. abortus contributes to the activation of the blood\u2013brain barrier in neurobrucellosis and IL-1\u03b2 mediates this phenomenon.<\/jats:p>","DOI":"10.4049\/jimmunol.1500908","type":"journal-article","created":{"date-parts":[[2016,3,17]],"date-time":"2016-03-17T02:29:05Z","timestamp":1458181745000},"page":"3794-3805","source":"Crossref","is-referenced-by-count":33,"title":["Glial Cell\u2013Elicited Activation of Brain Microvasculature in Response to <i>Brucella abortus<\/i> Infection Requires ASC Inflammasome\u2013Dependent IL-1\u03b2 Production"],"prefix":"10.1093","volume":"196","author":[{"given":"M Cruz","family":"Miraglia","sequence":"first","affiliation":[{"name":"Institute of Immunology, Genetics and Metabolism (National Scientific and Technical Research Council\/University of Buenos Aires), Clinical Hospital Jos\u00e9 de San Mart\u00edn, Faculty of Medicine, University of Buenos Aires , Buenos Aires C1120AAR ,","place":["Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam M","family":"Costa Franco","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais , Belo Horizonte-Minas Gerais 31270-901 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana M","family":"Rodriguez","sequence":"additional","affiliation":[{"name":"Institute of Immunology, Genetics and Metabolism (National Scientific and Technical Research Council\/University of Buenos Aires), Clinical Hospital Jos\u00e9 de San Mart\u00edn, Faculty of Medicine, University of Buenos Aires , Buenos Aires C1120AAR ,","place":["Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6976-9633","authenticated-orcid":false,"given":"Paula M 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