{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T21:44:55Z","timestamp":1792100695018,"version":"4.4.0"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2006,3,1]],"date-time":"2006-03-01T00:00:00Z","timestamp":1141171200000},"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":[[2006,3,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Infection of human monocyte-derived macrophages with Mycobacterium tuberculosis at low multiplicities of infection leads 48\u201372 h after the infection to cell death with the characteristics of apoptosis or necrosis. Predominant induction of one or the other cell death modality depends on differences in mitochondrial membrane perturbation induced by attenuated and virulent strains. Infection of macrophages with the attenuated H37Ra or the virulent H37Rv causes mitochondrial outer membrane permeabilization characterized by cytochrome c release from the mitochondrial intermembrane space and apoptosis. Mitochondrial outer membrane permeabilization is transient, peaks 6 h after infection, and requires Ca2+ flux and B cell chronic lymphocytic leukemia\/lymphoma 2-associated protein X translocation into mitochondria. In contrast, only the virulent H37Rv induces significant mitochondrial transmembrane potential (\u0394\u03c8m) loss caused by mitochondrial permeability transition. Dissipation of \u0394\u03c8m also peaks at 6 h after infection, is transient, is inhibited by the classical mitochondrial permeability transition inhibitor cyclosporine A, has a requirement for mitochondrial Ca2+ loading, and is independent of B cell chronic lymphocytic leukemia\/lymphoma translocation into the mitochondria. Transient dissipation of \u0394\u03c8m 6 h after infection is essential for the induction of macrophage necrosis by Mtb, a mechanism that allows further dissemination of the pathogen and development of the disease.<\/jats:p>","DOI":"10.4049\/jimmunol.176.6.3707","type":"journal-article","created":{"date-parts":[[2014,4,20]],"date-time":"2014-04-20T19:34:33Z","timestamp":1398022473000},"page":"3707-3716","source":"Crossref","is-referenced-by-count":228,"title":["A Mechanism of Virulence: Virulent\n                    <i>Mycobacterium tuberculosis<\/i>\n                    Strain H37Rv, but Not Attenuated H37Ra, Causes Significant Mitochondrial Inner Membrane Disruption in Macrophages Leading to Necrosis"],"prefix":"10.1093","volume":"176","author":[{"given":"Minjian","family":"Chen","sequence":"first","affiliation":[{"name":"Division of Rheumatology\/Immunology, Department of Medicine, Medical Research Center Brigham and Women\u2019s Hospital, Harvard Medical School , Boston, MA 02115"},{"name":"Clinical Research Center, First Affiliated Hospital, Guangxi Medical University , Nanning, Guangxi, 530021 ,","place":["People\u2019s Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huixian","family":"Gan","sequence":"additional","affiliation":[{"name":"Division of Rheumatology\/Immunology, Department of Medicine, Medical Research Center Brigham and Women\u2019s Hospital, Harvard Medical School , Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heinz G","family":"Remold","sequence":"additional","affiliation":[{"name":"Division of Rheumatology\/Immunology, Department of Medicine, Medical Research Center Brigham and Women\u2019s Hospital, Harvard Medical School , Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2006,3,15]]},"reference":[{"key":"2026020214071245300_R1","first-page":"1009","volume-title":"Arch. 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