{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T12:56:59Z","timestamp":1791205019550,"version":"4.1.0"},"reference-count":65,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2006,9,1]],"date-time":"2006-09-01T00:00:00Z","timestamp":1157068800000},"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":[[2006,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p><jats:italic>Brucella<\/jats:italic>spp. are facultative intracellular bacteria that cause brucellosis in humans and other animals.<jats:italic>Brucella<\/jats:italic>spp. are taken up by macrophages, and the outcome of the macrophage-<jats:italic>Brucella<\/jats:italic>interaction is a basis for establishment of a chronic<jats:italic>Brucella<\/jats:italic>infection. Microarrays were used to analyze the transcriptional response of the murine macrophage-like J774.A1 cell line to infection with virulent<jats:italic>Brucella melitensis<\/jats:italic>strain 16M. It was found that most significant changes in macrophage gene transcription happened early following infection, and global macrophage gene expression profiles returned to normal between 24 and 48 h postinfection. These findings support the observation that macrophages kill the majority of<jats:italic>Brucella<\/jats:italic>cells at the early infection stage, but the surviving<jats:italic>Brucella<\/jats:italic>cells are able to avoid macrophage brucellacidal activity inside replicative phagosomes at the later infection stage. At 4 h postinfection, macrophage genes involved in cell growth, metabolism, and responses to endogenous stimuli were down-regulated, while the inflammatory response (e.g., tumor necrosis factor alpha and Toll-like receptor 2), the complement system, the responses to external stimuli, and other immune responses were up-regulated. It is likely that the most active brucellacidal activity happened between 0 and 4 h postinfection. Mitochondrion-associated gene expression, which is involved in protein synthesis and transport, electron transfer, and small-molecule transfer, and many other mitochondrial functions were significantly down-regulated at 4 h postinfection. Although there were both pro- and antiapoptosis effects,<jats:italic>B. melitensis<\/jats:italic>16M appears to inhibit apoptosis of macrophages by blocking release of cytochrome<jats:italic>c<\/jats:italic>and production of reactive oxygen species in the mitochondria, thus preventing activation of caspase cascades.<\/jats:p>","DOI":"10.1128\/iai.01998-05","type":"journal-article","created":{"date-parts":[[2006,8,22]],"date-time":"2006-08-22T22:13:07Z","timestamp":1156284787000},"page":"5035-5046","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":93,"title":["<i>Brucella melitensis<\/i>Triggers Time-Dependent Modulation of Apoptosis and Down-Regulation of Mitochondrion-Associated Gene Expression in Mouse Macrophages"],"prefix":"10.1128","volume":"74","author":[{"given":"Yongqun","family":"He","sequence":"first","affiliation":[{"name":"Unit for Laboratory Animal Medicine and Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sherry","family":"Reichow","sequence":"additional","affiliation":[{"name":"Analytical Services Inc., 2900 South Quincy Street, Homeland Security Institute, Arlington, Virginia 22206"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheela","family":"Ramamoorthy","sequence":"additional","affiliation":[{"name":"Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24061"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xicheng","family":"Ding","sequence":"additional","affiliation":[{"name":"Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24061"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raju","family":"Lathigra","sequence":"additional","affiliation":[{"name":"Department of Bacterial Diseases, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, Maryland 20910"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna C.","family":"Craig","sequence":"additional","affiliation":[{"name":"Virginia Bioinformatics Institute, Virginia Polytechnic Institute and State University, Washington Street, Blacksburg, Virginia 24061"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno W. S.","family":"Sobral","sequence":"additional","affiliation":[{"name":"Virginia Bioinformatics Institute, Virginia Polytechnic Institute and State University, Washington Street, Blacksburg, Virginia 24061"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerhardt G.","family":"Schurig","sequence":"additional","affiliation":[{"name":"Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24061"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nammalwar","family":"Sriranganathan","sequence":"additional","affiliation":[{"name":"Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24061"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen M.","family":"Boyle","sequence":"additional","affiliation":[{"name":"Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24061"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","unstructured":"Affymetrix. 2004. GeneChip expression data analysis fundamentals. Affymetrix Inc. Santa Clara CA."},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V93.4.1277"},{"key":"e_1_3_2_4_2","first-page":"165","volume":"358","year":"2002","unstructured":"Andersson, S. G., K. O., Canback, B., Kurland, and C. G. 2002. On the origin of mitochondria: a genomics perspective. Philos. Trans. R. Soc. Lond. B Biol. Sci.358:165-177.","journal-title":"Philos. Trans. R. Soc. Lond. B Biol. Sci."},{"key":"e_1_3_2_5_2","first-page":"25","volume":"25","year":"2000","unstructured":"Ashburner, M., C. A. Ball, J. A. Blake, D. Botstein, H. Butler, J. M. Cherry, A. P. Davis, K. Dolinski, S. S. Dwight, J. T. Eppig, M. A. Harris, D. P. Hill, L. Issel-Tarver, A. Kasarskis, S. Lewis, J. C. Matese, J. E. Richardson, M. Ringwald, G. M. Rubin, and G. Sherlock. 2000. Gene ontology: tool for the unification of biology. The Gene Ontology Consortium. Nat. Genet.25:25-29.","journal-title":"The Gene Ontology Consortium. Nat. Genet."},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0278-5846(03)00016-2"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.74.12.5470-5476.2000"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-1135(02)00219-5"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/0076-6879(94)36039-1"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.178.11.3015-3024.1996"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-1135(02)00228-6"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.1.176-186.2004"},{"key":"e_1_3_2_13_2","doi-asserted-by":"crossref","first-page":"2885","DOI":"10.4049\/jimmunol.156.8.2885","volume":"156","year":"1996","unstructured":"Caron, E., A. Gross, J. P. Liautard, and J. Dornand. 1996. Brucella species release a specific, protease-sensitive, inhibitor of TNF-alpha expression, active on human macrophage-like cells. J. Immunol.156:2885-2893.","journal-title":"J. Immunol."},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1080\/15216540152845984"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20030088"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.184.4.1349"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc883"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1462-5822.2001.00131.x"},{"key":"e_1_3_2_19_2","doi-asserted-by":"crossref","first-page":"1658","DOI":"10.2460\/ajvr.1991.52.10.1658","volume":"52","year":"1991","unstructured":"Detilleux, P. G., B. L. Deyoe, and N. F. Cheville. 1991. Effect of endocytic and metabolic inhibitors on the internalization and intracellular growth of Brucella abortus in Vero cells. Am. J. Vet. Res.52:1658-1664.","journal-title":"Am. J. Vet. Res."},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-1135(02)00223-7"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.63.9.3297-3301.1995"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2004.03.002"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1089\/153623103322006661"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.71.3.1125-1133.2003"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.68.1.257-263.2000"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.71.4.2110-2119.2003"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.173.7.4635"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-1135(02)00214-6"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.68.1.342-351.2000"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M105606200"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.171.3.1441"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-06-1918"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.61.1.124-134.1993"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1006\/cimm.1993.1121"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.73.011303.073706"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.60.7.3011-3014.1992"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.232454299"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0966-842X(03)00078-7"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-1135(02)00215-8"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4400991"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.45.29451"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(04)00088-7"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1205862"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-1135(02)00218-3"},{"key":"e_1_3_2_46_2","unstructured":"Manual G. 2003. GeneSpring version 7.0 manual. Silicon Genetics. Redwood City CA."},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1432-1327.1998.2520001.x"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1999.5800"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.022622699"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-695X.2001.tb00536.x"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/16.15.4650"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.1.440-450.2004"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2004.02572.x"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1266"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-9877(98)90252-3"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0854.2002.31007.x"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2004.04017.x"},{"key":"e_1_3_2_58_2","first-page":"365","volume":"132","year":"2000","unstructured":"Rozen, S., and H. Skaletsky. 2000. Primer3 on the WWW for general users and for biologist programmers. Methods Mol. Biol.132:365-386.","journal-title":"Methods Mol. Biol."},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1385\/CBB:39:3:279"},{"key":"e_1_3_2_60_2","unstructured":"Silicon Genetics. 2003. Statistical analysis (1-way ANOVA). [Online.] Silicon Genetics Redwood City CA. http:\/\/www.silicongenetics.com ."},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1002\/1521-4141(200204)32:4<1059::AID-IMMU1059>3.0.CO;2-G"},{"key":"e_1_3_2_62_2","first-page":"135","year":"1988","unstructured":"Timoney, J. F., J. H. Gillespie, F. W. Scott, and J. E. Barlough. 1988. The genus Brucella, p. 135-152. InHagan and Bruner's microbiology and infectious diseases of domestic animals, 8th ed. Cornell University Press, Ithaca, NY.","journal-title":"Hagan and Bruner's microbiology and infectious diseases of domestic animals"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M212374200"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.1.144"},{"key":"e_1_3_2_65_2","unstructured":"Wise D. J. 1995. Intracellular growth of Brucella abortus and B. melitensis in murine macrophage-like cell lines and partial characterization of a biologically active extract from B. abortus strain RB51. Ph.D. dissertation. Virginia Polytechnic Institute and State University Blacksburg."},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-2478(01)00326-1"}],"container-title":["Infection and Immunity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/IAI.01998-05","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/IAI.01998-05","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,6]],"date-time":"2024-02-06T02:03:47Z","timestamp":1707185027000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/IAI.01998-05"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,9]]},"references-count":65,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2006,9]]}},"alternative-id":["10.1128\/IAI.01998-05"],"URL":"https:\/\/doi.org\/10.1128\/iai.01998-05","relation":{},"ISSN":["0019-9567","1098-5522"],"issn-type":[{"value":"0019-9567","type":"print"},{"value":"1098-5522","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,9]]},"assertion":[{"value":"2005-12-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2006-06-05","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2006-09-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}