MicroRNA-27a controls the intracellular survival of Mycobacterium tuberculosis by regulating calcium-associated autophagy.
MicroRNA-27a controls the intracellular survival of Mycobacterium tuberculosis by regulating calcium-associated autophagy.
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MicroRNA-27a 通过调节钙相关自噬来控制结核分枝杆菌的细胞内存活
DOI：
10.1038/s41467-018-06836-4
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发表时间：
2018-10-16
影响因子：
16.6
通讯作者：
Ge B
中科院分区：
文献类型：
--
作者：
Liu F;Chen J;Wang P;Li H;Zhou Y;Liu H;Liu Z;Zheng R;Wang L;Yang H;Cui Z;Wang F;Huang X;Wang J;Sha W;Xiao H;Ge B
由结核分枝杆菌（Mycobacterium tuberculosis，Mtb）引起的结核病每年造成数百万人死亡，耐药结核病的快速发展迫切需要开发新型抗结核药物。虽然自噬调节Mtb的细胞内存活，但在Mtb感染期间钙（Ca 2+）信号传导在调节自噬中的作用仍然在很大程度上未知。在这里，我们发现microRNA miR-27 a在活动性结核病患者、结核分枝杆菌感染的小鼠和巨噬细胞中大量表达。miR-27 a的靶点是位于ER的Ca 2+转运蛋白CACNA 2D 3。靶向该转运蛋白导致Ca 2+信号转导下调，从而抑制自噬体形成并促进Mtb的细胞内存活。缺乏miR-27 a的小鼠和用针对miR-27 a的Escheromir治疗的小鼠对Mtb感染更具抗性。我们的研究结果揭示了Mtb通过操纵Ca 2+相关的自噬来增加细胞内存活的策略，并且也可能支持宿主导向的抗TB治疗方法的发展。结核分枝杆菌（Mtb）如何逃脱自噬介导的清除知之甚少。在这里，Liu等人表明Mtb诱导的MicroRNA-27 a靶向ER相关的钙转运蛋白CACNA 2D 3，导致抗微生物自噬的抑制和Mtb细胞内存活的增强。
Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) kills millions every year, and there is urgent need to develop novel anti-TB agents due to the fast-growing of drug-resistant TB. Although autophagy regulates the intracellular survival of Mtb, the role of calcium (Ca2+) signaling in modulating autophagy during Mtb infection remains largely unknown. Here, we show that microRNA miR-27a is abundantly expressed in active TB patients, Mtb-infected mice and macrophages. The target of miR-27a is the ER-located Ca2+ transporter CACNA2D3. Targeting of this transporter leads to the downregulation of Ca2+ signaling, thus inhibiting autophagosome formation and promoting the intracellular survival of Mtb. Mice lacking of miR-27a and mice treated with an antagomir to miR-27a are more resistant to Mtb infection. Our findings reveal a strategy for Mtb to increase intracellular survival by manipulating the Ca2+-associated autophagy, and may also support the development of host-directed anti-TB therapeutic approaches. How Mycobacterium tuberculosis (Mtb) escapes autophagy-mediated clearance is poorly understood. Here, Liu et al. show that Mtb-induced MicroRNA-27a targets the ER-associated calcium transporter CACNA2D3, leading to suppression of antimicrobial autophagy and to enhanced intracellular survival of Mtb.
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影响因子：
21.3
作者：
通讯作者：
--
影响因子：
4.9
作者：
Kelly, BP;Furney, SK;Orme, IM
通讯作者：
Orme, IM
DOI：
10.1073/pnas.1210500109
发表时间：
2012-11-13
影响因子：
11.1
作者：
Castillo, Eliseo F.;Dekonenko, Alexander;Deretic, Vojo
通讯作者：
Deretic, Vojo
影响因子：
6.4
作者：
Horne, David J.;Graustein, Andrew D.;Hawn, Thomas R.
通讯作者：
Hawn, Thomas R.
影响因子：
64.8
作者：
Kimmey JM;Huynh JP;Weiss LA;Park S;Kambal A;Debnath J;Virgin HW;Stallings CL
通讯作者：
Stallings CL