Tropheryma whipplei, the Whipple's disease bacillus, induces macrophage apoptosis through the extrinsic pathway.
Tropheryma whipplei, the Whipple's disease bacillus, induces macrophage apoptosis through the extrinsic pathway.
复制标题
惠普尔氏杆菌（Tropheryma whipplei）通过外在途径诱导巨噬细胞凋亡。
DOI：
10.1038/cddis.2010.11
复制
发表时间：
2010-04-08
影响因子：
9
通讯作者：
中科院分区：
文献类型：
--
作者：
惠普尔滋养体是维普莱病的病原体，是一种感染巨噬细胞的细胞内细菌。我们先前表明，感染的巨噬细胞的结果在M2极化与诱导细胞凋亡和白细胞介素（IL）-16分泌。在患有维普莱病的患者中，细胞凋亡标记物和IL-16的循环水平增加，并且与疾病的活动性相关。为了深入了解这种罕见疾病的病理生理学，我们研究了T。Whipplei诱导的人巨噬细胞凋亡。我们的数据表明，细胞凋亡诱导依赖于细菌的生存能力，抑制细菌蛋白质的合成减少了T。惠普尔。细胞凋亡的诱导也与促凋亡和抗凋亡介质的大量降解有关。胱天蛋白酶特异性抑制实验表明，启动子胱天蛋白酶8和10所需的凋亡，相反，胱天蛋白酶2和9，尽管细胞色素C从线粒体释放。最后，效应器半胱天冬酶3和6是强制性的凋亡诱导。总的来说，这些数据表明，T。whipplei通过外源性途径诱导细胞凋亡，并且除了巨噬细胞的M2极化之外，细胞凋亡诱导有助于细菌复制，并且代表这种细胞内病原体的毒力特征。
Tropheryma whipplei, the etiological agent of Whipple's disease, is an intracellular bacterium that infects macrophages. We previously showed that infection of macrophages results in M2 polarization associated with induction of apoptosis and interleukin (IL)-16 secretion. In patients with Whipple's disease, circulating levels of apoptotic markers and IL-16 are increased and correlate with the activity of the disease. To gain insight into the understanding of the pathophysiology of this rare disease, we examined the molecular pathways involved in T. whipplei-induced apoptosis of human macrophages. Our data showed that apoptosis induction depended on bacterial viability and inhibition of bacterial protein synthesis reduced the apoptotic program elicited by T. whipplei. Induction of apoptosis was also associated with a massive degradation of both pro- and anti-apoptotic mediators. Caspase-specific inhibition experiments revealed that initiator caspases 8 and 10 were required for apoptosis, in contrast to caspases 2 and 9, in spite of cytochrome-c release from mitochondria. Finally, the effector caspases 3 and 6 were mandatory for apoptosis induction. Collectively, these data suggest that T. whipplei induces apoptosis through the extrinsic pathway and that, beside M2 polarization of macrophages, apoptosis induction contributes to bacterial replication and represents a virulence trait of this intracellular pathogen.
登录
查看更多内容
影响因子：
6.4
作者：
Desnues, B;Lepidi, H;Mege, JL
通讯作者：
Mege, JL
影响因子：
11.4
作者：
Asada, M;Yamada, T;Mizutani, S
通讯作者：
Mizutani, S
影响因子：
3.7
作者：
Benoit M;Fenollar F;Raoult D;Mege JL
通讯作者：
Mege JL
DOI：
10.1073/pnas.90.21.10198
发表时间：
1993-11-01
影响因子：
11.1
作者：
HANNA, PC;ACOSTA, D;COLLIER, RJ
通讯作者：
COLLIER, RJ
影响因子：
6.7
作者：
Benoit M;Ghigo E;Capo C;Raoult D;Mege JL
通讯作者：
Mege JL