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Brucella abortus is the causative agent of brucellosis, a debilitating disease that affects humans and animals. In this study, we demonstrate that C57BL\/6 mouse bone marrow\u2013derived macrophages under BCG training enhance inflammatory responses against B. abortus. BCG-trained macrophages showed increased MHC class II and CD40 expression on the cell surface and higher IL-6, IL-12, and IL-1\u03b2 production. The increase in IL-1\u03b2 secretion was accompanied by enhanced activation of canonical and noncanonical inflammasome platforms. We observed elevated caspase-11 expression and caspase-1 processing in BCG-trained macrophages in response to B. abortus compared with untrained cells. In addition, these BCG-trained cells showed higher NLRP3 expression after B. abortus infection. From a metabolic point of view, signaling through the Akt\/mammalian target of rapamycin\/S6 kinase pathway was also enhanced. In addition, BCG training resulted in higher inducible NO synthase expression and nitrite production, culminating in an improved macrophage-killing capacity against intracellular B. abortus. In vivo, we monitored a significant reduction in the bacterial burden in organs from BCG-trained C57BL\/6 mice when compared with the untrained group. In addition, previous BCG immunization of RAG-1\u2013deficient mice partially protects against Brucella infection, suggesting the important role of the innate immune compartment in this scenario. Furthermore, naive recipient mice that received BM transfer from BCG-trained donors showed greater resistance to B. abortus when compared with their untrained counterparts. These results demonstrate that BCG-induced trained immunity in mice results in better control of intracellular B. abortus in vivo and in vitro.<\/jats:p>","DOI":"10.4049\/jimmunol.2200642","type":"journal-article","created":{"date-parts":[[2023,7,21]],"date-time":"2023-07-21T10:54:32Z","timestamp":1689936872000},"page":"791-803","source":"Crossref","is-referenced-by-count":14,"title":["Bacillus Calmette-Gu\u00e9rin\u2013Trained Macrophages Elicit a Protective Inflammatory Response against the Pathogenic Bacteria\n                    <i>Brucella abortus<\/i>"],"prefix":"10.1093","volume":"211","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1045-2249","authenticated-orcid":false,"given":"Ana Carolina V S C","family":"de Araujo","sequence":"first","affiliation":[{"name":"Departamento de Gen\u00e9tica, Ecologia e Evolu\u00e7\u00e3o, Programa de P\u00f3s-Gradua\u00e7\u00e3o em Gen\u00e9tica, Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Minas Gerais , Belo Horizonte, Minas Gerais ,","place":["Brazil"]},{"name":"Departamento de Bioqu\u00edmica e Imunologia, Programa de P\u00f3s-Gradua\u00e7\u00e3o em Bioqu\u00edmica e Imunologia, Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Minas Gerais , Belo Horizonte, Minas Gerais ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9789-1035","authenticated-orcid":false,"given":"Nina M G P","family":"de Queiroz","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica e Imunologia, Programa de P\u00f3s-Gradua\u00e7\u00e3o em Bioqu\u00edmica e Imunologia, Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Minas Gerais , Belo Horizonte, Minas Gerais ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6885-3438","authenticated-orcid":false,"given":"F\u00e1bio V","family":"Marinho","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica e Imunologia, Programa de P\u00f3s-Gradua\u00e7\u00e3o em Bioqu\u00edmica e Imunologia, Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Minas Gerais , Belo Horizonte, Minas Gerais ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4062-5577","authenticated-orcid":false,"given":"Sergio C","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Departamento de Gen\u00e9tica, Ecologia e Evolu\u00e7\u00e3o, Programa de P\u00f3s-Gradua\u00e7\u00e3o em Gen\u00e9tica, Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Minas Gerais , Belo Horizonte, Minas Gerais ,","place":["Brazil"]},{"name":"Departamento de Bioqu\u00edmica e Imunologia, Programa de P\u00f3s-Gradua\u00e7\u00e3o em Bioqu\u00edmica e Imunologia, Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Minas Gerais , Belo Horizonte, Minas Gerais ,","place":["Brazil"]},{"name":"Departamento de Imunologia, Instituto de Ci\u00eancias Biom\u00e9dicas, Universidade de S\u00e3o Paulo , S\u00e3o Paulo ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,7,21]]},"reference":[{"key":"2026041420284220600_r1","doi-asserted-by":"crossref","first-page":"e148291","DOI":"10.1172\/JCI148291","article-title":"BCG turns 100: its nontraditional uses against viruses, cancer, and immunologic diseases","volume":"131","author":"Singh","year":"2021","journal-title":"J. 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