{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T19:09:54Z","timestamp":1791054594394,"version":"4.1.0"},"reference-count":62,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2013,4,1]],"date-time":"2013-04-01T00:00:00Z","timestamp":1364774400000},"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":[[2013,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Pathogens are detected by innate immune receptors that, upon activation, orchestrate an appropriate immune response. Recent studies revealed the intracellular signaling cascades involved in the TLR-initiated immune response to Brucella abortus infection. However, no report has elucidated the role of inflammasome receptors in Brucella recognition. Therefore, we decided to investigate the function of NLRC4, NLRP3, and AIM2 in sensing Brucella. In this study, we showed that NLRC4 is not required to induce caspase-1 activation and further secretion of IL-1\u03b2 by B. abortus in macrophages. In contrast, we determined that AIM2, which senses Brucella DNA, and NLRP3 are partially required for caspase-1 activation and IL-1\u03b2 secretion. Additionally, mitochondrial reactive oxygen species induced by Brucella were implicated in IL-1\u03b2 production. Furthermore, AIM2, NLRP3, ASC, and caspase-1 knockout mice were more susceptible to B. abortus infection than were wild-type animals, suggesting that multiple ASC-dependent inflammasomes contribute to host protection against infection. This protective effect is due to the inflammatory response caused by IL-1\u03b2 and IL-18 rather than pyroptosis, because we observed augmented bacterial burden in IL-1R and IL-18 knockout mice. Finally, we determined that bacterial type IV secretion system VirB and live, but not heat-killed, Brucella are required for full inflammasome activation in macrophages during infection. Taken together, our results indicate that Brucella is sensed by ASC inflammasomes that collectively orchestrate a robust caspase-1 activation and proinflammatory response.<\/jats:p>","DOI":"10.4049\/jimmunol.1202817","type":"journal-article","created":{"date-parts":[[2013,3,5]],"date-time":"2013-03-05T11:06:38Z","timestamp":1362481598000},"page":"3629-3638","source":"Crossref","is-referenced-by-count":115,"title":["Critical Role of ASC Inflammasomes and Bacterial Type IV Secretion System in Caspase-1 Activation and Host Innate Resistance to <i>Brucella abortus<\/i> Infection"],"prefix":"10.1093","volume":"190","author":[{"given":"Marco Tulio R","family":"Gomes","sequence":"first","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":"Priscila C","family":"Campos","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":"Fernanda S","family":"Oliveira","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":"Patricia P","family":"Corsetti","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":"Karina R","family":"Bortoluci","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Center of Molecular and Cellular Therapy, Federal University of S\u00e3o Paulo , Diadema, S\u00e3o Paulo, 04044-010","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larissa D","family":"Cunha","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, School of Medicine of Ribeir\u00e3o Preto-S\u00e3o Paulo, University of S\u00e3o Paulo , Ribeir\u00e3o Preto, 14049-900","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dario S","family":"Zamboni","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, School of Medicine of Ribeir\u00e3o Preto-S\u00e3o Paulo, University of S\u00e3o Paulo , Ribeir\u00e3o Preto, 14049-900","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio C","family":"Oliveira","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"}]}],"member":"286","published-online":{"date-parts":[[2013,4,1]]},"reference":[{"key":"2025032406495814900_r1","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1016\/j.immuni.2011.05.006","article-title":"Toll-like receptors and their crosstalk with other innate receptors in infection and immunity","volume":"34","author":"Kawai","year":"2011","journal-title":"Immunity"},{"key":"2025032406495814900_r2","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1146\/annurev.immunol.021908.132612","article-title":"Immunological and inflammatory functions of the interleukin-1 family","volume":"27","author":"Dinarello","year":"2009","journal-title":"Annu. 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