Attenuated Mycobacterium tuberculosis SO2 vaccine candidate is unable to induce cell death.
Attenuated Mycobacterium tuberculosis SO2 vaccine candidate is unable to induce cell death.
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DOI：
10.1371/journal.pone.0045213
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Pardo J
中科院分区：
文献类型：
--
作者：
Aporta A;Arbues A;Aguilo JI;Monzon M;Badiola JJ;de Martino A;Ferrer N;Marinova D;Anel A;Martin C;Pardo J
有人提出，结核分枝杆菌强毒菌株通过宿主巨噬细胞坏死来抑制细胞凋亡并引发细胞死亡，以逃避先天免疫，而非强毒菌株则诱导典型的细胞凋亡，激活保护性宿主反应。作为新型结核病候选疫苗（结核分枝杆菌 phoP 突变体 SO2）表征的一部分，我们试图评估其诱导宿主细胞死亡的潜力。亲本结核分枝杆菌 MT103 菌株和当前的抗结核卡介苗 (BCG) 疫苗被用作体外和体内小鼠模型的比较物。我们的数据表明，减毒 SO2 在体外小鼠巨噬细胞中和体内肺部感染期间均不能诱导细胞凋亡事件。相比之下，有毒的 MT103 会引发典型的细胞凋亡事件，包括磷脂酰丝氨酸暴露、caspase-3 激活以及核浓缩和断裂。 BCG 菌株的行为与 SO2 相似，不会诱导细胞凋亡。克隆存活测定证实，BCG 或 SO2 感染的巨噬细胞的活力不受影响。我们的结果放弃了细胞凋亡作为 SO2 疫苗诱导的保护机制，并为经典细胞凋亡诱导与毒力菌株之间的正相关性提供了证据，表明细胞凋亡可能是结核分枝杆菌感染期间的毒力决定因素。
It has been proposed that Mycobacterium tuberculosis virulent strains inhibit apoptosis and trigger cell death by necrosis of host macrophages to evade innate immunity, while non-virulent strains induce typical apoptosis activating a protective host response. As part of the characterization of a novel tuberculosis vaccine candidate, the M. tuberculosis phoP mutant SO2, we sought to evaluate its potential to induce host cell death. The parental M. tuberculosis MT103 strain and the current vaccine against tuberculosis Bacillus Calmette-Guérin (BCG) were used as comparators in mouse models in vitro and in vivo. Our data reveal that attenuated SO2 was unable to induce apoptotic events neither in mouse macrophages in vitro nor during lung infection in vivo. In contrast, virulent MT103 triggers typical apoptotic events with phosphatidylserine exposure, caspase-3 activation and nuclear condensation and fragmentation. BCG strain behaved like SO2 and did not induce apoptosis. A clonogenic survival assay confirmed that viability of BCG- or SO2-infected macrophages was unaffected. Our results discard apoptosis as the protective mechanism induced by SO2 vaccine and provide evidence for positive correlation between classical apoptosis induction and virulent strains, suggesting apoptosis as a possible virulence determinant during M. tuberculosis infection.
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影响因子：
3.7
作者：
Ferrer, Nadia L.;Gomez, Ana B.;Martin, Carlos
通讯作者：
Martin, Carlos
DOI：
10.1084/jem.20080767
发表时间：
2008-11-24
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Chen M;Divangahi M;Gan H;Shin DS;Hong S;Lee DM;Serhan CN;Behar SM;Remold HG
通讯作者：
Remold HG
影响因子：
6.7
作者：
Astarie-Dequeker C;Le Guyader L;Malaga W;Seaphanh FK;Chalut C;Lopez A;Guilhot C
通讯作者：
Guilhot C
影响因子：
6.4
作者：
Gil, DP;León, LG;Rojas, M
通讯作者：
Rojas, M
影响因子：
4.4
作者：
Chen, Minjian;Gan, Huixian;Remold, Heinz G.
通讯作者：
Remold, Heinz G.