The balance of apoptotic and necrotic cell death in Mycobacterium tuberculosis infected macrophages is not dependent on bacterial virulence.
<h4>Background</h4>An important mechanism of Mycobacterium tuberculosis pathogenesis is the ability to control cell death pathways in infected macrophages: apoptotic cell death is bactericidal, whereas necrotic cell death may facilitate bacterial dissemination and transmission.<h4>...
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0047573&type=printable |
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| author | Rachel E Butler Priscille Brodin Jichan Jang Mi-Seon Jang Brian D Robertson Brigitte Gicquel Graham R Stewart |
| author_facet | Rachel E Butler Priscille Brodin Jichan Jang Mi-Seon Jang Brian D Robertson Brigitte Gicquel Graham R Stewart |
| author_sort | Rachel E Butler |
| collection | DOAJ |
| description | <h4>Background</h4>An important mechanism of Mycobacterium tuberculosis pathogenesis is the ability to control cell death pathways in infected macrophages: apoptotic cell death is bactericidal, whereas necrotic cell death may facilitate bacterial dissemination and transmission.<h4>Methods</h4>We examine M.tuberculosis control of spontaneous and chemically induced macrophage cell death using automated confocal fluorescence microscopy, image analysis, flow cytometry, plate-reader based vitality assays, and M.tuberculosis strains including H37Rv, and isogenic virulent and avirulent strains of the Beijing lineage isolate GC1237.<h4>Results</h4>We show that bacterial virulence influences the dynamics of caspase activation and the total level of cytotoxicity. We show that the powerful ability of M.tuberculosis to inhibit exogenously stimulated apoptosis is abrogated by loss of virulence. However, loss of virulence did not influence the balance of macrophage apoptosis and necrosis--both virulent and avirulent isogenic strains of GC1237 induced predominantly necrotic cell death compared to H37Rv which induced a higher relative level of apoptosis.<h4>Conclusions</h4>This reveals that macrophage necrosis and apoptosis are independently regulated during M. tuberculosis infection of macrophages. Virulence affects the level of host cell death and ability to inhibit apoptosis but other strain-specific characteristics influence the ultimate mode of host cell death and alter the balance of apoptosis and necrosis. |
| format | Article |
| id | doaj-art-cc3a9b9321e74dadbb0ee5c2a12e90ed |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
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| spelling | doaj-art-cc3a9b9321e74dadbb0ee5c2a12e90ed2025-08-20T02:05:35ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-01710e4757310.1371/journal.pone.0047573The balance of apoptotic and necrotic cell death in Mycobacterium tuberculosis infected macrophages is not dependent on bacterial virulence.Rachel E ButlerPriscille BrodinJichan JangMi-Seon JangBrian D RobertsonBrigitte GicquelGraham R Stewart<h4>Background</h4>An important mechanism of Mycobacterium tuberculosis pathogenesis is the ability to control cell death pathways in infected macrophages: apoptotic cell death is bactericidal, whereas necrotic cell death may facilitate bacterial dissemination and transmission.<h4>Methods</h4>We examine M.tuberculosis control of spontaneous and chemically induced macrophage cell death using automated confocal fluorescence microscopy, image analysis, flow cytometry, plate-reader based vitality assays, and M.tuberculosis strains including H37Rv, and isogenic virulent and avirulent strains of the Beijing lineage isolate GC1237.<h4>Results</h4>We show that bacterial virulence influences the dynamics of caspase activation and the total level of cytotoxicity. We show that the powerful ability of M.tuberculosis to inhibit exogenously stimulated apoptosis is abrogated by loss of virulence. However, loss of virulence did not influence the balance of macrophage apoptosis and necrosis--both virulent and avirulent isogenic strains of GC1237 induced predominantly necrotic cell death compared to H37Rv which induced a higher relative level of apoptosis.<h4>Conclusions</h4>This reveals that macrophage necrosis and apoptosis are independently regulated during M. tuberculosis infection of macrophages. Virulence affects the level of host cell death and ability to inhibit apoptosis but other strain-specific characteristics influence the ultimate mode of host cell death and alter the balance of apoptosis and necrosis.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0047573&type=printable |
| spellingShingle | Rachel E Butler Priscille Brodin Jichan Jang Mi-Seon Jang Brian D Robertson Brigitte Gicquel Graham R Stewart The balance of apoptotic and necrotic cell death in Mycobacterium tuberculosis infected macrophages is not dependent on bacterial virulence. PLoS ONE |
| title | The balance of apoptotic and necrotic cell death in Mycobacterium tuberculosis infected macrophages is not dependent on bacterial virulence. |
| title_full | The balance of apoptotic and necrotic cell death in Mycobacterium tuberculosis infected macrophages is not dependent on bacterial virulence. |
| title_fullStr | The balance of apoptotic and necrotic cell death in Mycobacterium tuberculosis infected macrophages is not dependent on bacterial virulence. |
| title_full_unstemmed | The balance of apoptotic and necrotic cell death in Mycobacterium tuberculosis infected macrophages is not dependent on bacterial virulence. |
| title_short | The balance of apoptotic and necrotic cell death in Mycobacterium tuberculosis infected macrophages is not dependent on bacterial virulence. |
| title_sort | balance of apoptotic and necrotic cell death in mycobacterium tuberculosis infected macrophages is not dependent on bacterial virulence |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0047573&type=printable |
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