{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T03:16:54Z","timestamp":1790392614749,"version":"4.1.0"},"reference-count":42,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2011,6,1]],"date-time":"2011-06-01T00:00:00Z","timestamp":1306886400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2011,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p><jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Brucella<\/jats:named-content>spp. are intracellular bacteria that cause an infectious disease called brucellosis in humans and many domestic and wildlife animals.<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">B. suis<\/jats:named-content>primarily infects pigs and is pathogenic to humans. The macrophage-<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Brucella<\/jats:named-content>interaction is critical for the establishment of a chronic<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Brucella<\/jats:named-content>infection. Our studies showed that smooth virulent<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">B. suis<\/jats:named-content>strain 1330 (S1330) prevented programmed cell death of infected macrophages and rough attenuated<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">B. suis<\/jats:named-content>strain VTRS1 (a vaccine candidate) induced strong macrophage cell death. To further investigate the mechanism of VTRS1-induced macrophage cell death, microarrays were used to analyze temporal transcriptional responses of murine macrophage-like J774.A1 cells infected with S1330 or VTRS1. In total 17,685 probe sets were significantly regulated based on the effects of strain, time and their interactions. A miniTUBA dynamic Bayesian network analysis predicted that VTRS1-induced macrophage cell death was mediated by a proinflammatory gene (the tumor necrosis factor alpha [TNF-\u03b1] gene), an NF-\u03baB pathway gene (the I\u03baB-\u03b1 gene), the caspase-2 gene, and several other genes. VTRS1 induced significantly higher levels of transcription of 40 proinflammatory genes than S1330. A Mann-Whitney U test confirmed the proinflammatory response in VTRS1-infected macrophages. Increased production of TNF-\u03b1 and interleukin 1\u03b2 (IL-1\u03b2) were also detected in the supernatants in VTRS1-infected macrophage cell culture. Hyperphosphorylation of I\u03baB-\u03b1 was observed in macrophages infected with VTRS1 but not S1330. The important roles of TNF-\u03b1 and I\u03baB-\u03b1 in VTRS1-induced macrophage cell death were further confirmed by individual inhibition studies. VTRS1-induced macrophage cell death was significantly inhibited by a caspase-2 inhibitor but not a caspase-1 inhibitor. The role of caspase-2 in regulating the programmed cell death of VTRS1-infected macrophages was confirmed in another study using caspase-2-knockout mice. In summary, VTRS1 induces a proinflammatory, caspase-2- and NF-\u03baB-mediated macrophage cell death. This unique cell death differs from apoptosis, which is not proinflammatory. It is also different from classical pyroptosis, which is caspase-1 mediated.<\/jats:p>","DOI":"10.1128\/iai.00050-11","type":"journal-article","created":{"date-parts":[[2011,4,5]],"date-time":"2011-04-05T02:50:44Z","timestamp":1301971844000},"page":"2460-2469","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":41,"title":["Proinflammatory Caspase-2-Mediated Macrophage Cell Death Induced by a Rough Attenuated Brucella suis Strain"],"prefix":"10.1128","volume":"79","author":[{"given":"Fang","family":"Chen","sequence":"first","affiliation":[{"name":"Unit for Laboratory Animal Medicine, University of Michigan Medical School, Ann Arbor, Michigan 48109"},{"name":"Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan 48109"},{"name":"Center for Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan 48109"},{"name":"Comprehensive Cancer Center, 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