The rodent malaria liver stage survives in the rapamycin-induced autophagosome of infected Hepa1-6 cells.
The rodent malaria liver stage survives in the rapamycin-induced autophagosome of infected Hepa1-6 cells.
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啮齿动物疟疾肝脏阶段在雷帕霉素诱导的受感染 Hepa1-6 细胞的自噬体中存活
DOI：
10.1038/srep38170
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发表时间：
2016-11-30
影响因子：
4.6
通讯作者：
Xu W
中科院分区：
文献类型：
--
作者：
Zhao C;Liu T;Zhou T;Fu Y;Zheng H;Ding Y;Zhang K;Xu W
据报道，感染肝细胞的非选择性自噬可以促进疟疾在肝脏阶段的发展，但感染肝细胞的选择性自噬后寄生虫的命运仍然不是很清楚。在这里，我们证实，子孢子感染可以诱导一个选择性的自噬样过程，靶向EEFs（外红细胞形式）在Hepa 1 -6。雷帕霉素治疗大大增强了EEFs中的这一过程和感染的Hepa 1 -6细胞的非选择性自噬，并增强了体内疟疾肝脏阶段的发展。虽然雷帕霉素促进了含有疟原虫的自噬体与溶酶体的融合，但自噬体内的一些寄生虫存活并正常复制。进一步的研究表明，受影响的自溶酶体的成熟受到极大的抑制。因此，除了先前描述的雷帕霉素诱导的肝细胞非选择性自噬的积极作用，我们提供的证据表明，EEFs在感染的肝细胞自噬体的生存也有助于雷帕霉素增强疟疾肝阶段的发展，可能是由于EEFs抑制自溶酶体成熟。这些数据表明，抑制自溶体成熟可能是疟疾肝期使用的一种新的逃避策略。
It has been reported that non-selective autophagy of infected hepatocytes could facilitate the development of malaria in the liver stage, but the fate of parasites following selective autophagy of infected hepatocytes is still not very clear. Here, we confirmed that sporozoite infection can induce a selective autophagy-like process targeting EEFs (exo-erythrocytic forms) in Hepa1–6. Rapamycin treatment greatly enhanced this process in EEFs and non-selective autophagy of infected Hepa1-6 cells and enhanced the development of the malaria liver stage in vivo. Although rapamycin promoted the fusion of autophagosomes containing the malaria parasite with lysosomes, some parasites inside the autophagosome survived and replicated normally. Further study showed that the maturation of affected autolysosomes was greatly inhibited. Therefore, in addition to the previously described positive role of rapamycin-induced nonselective autophagy of hepatocytes, we provide evidence that the survival of EEFs in the autophagosome of the infected hepatocytes also contributes to rapamycin-enhanced development of the malaria liver stage, possibly due to the suppression of autolysosome maturation by EEFs. These data suggest that the inhibition of autolysosome maturation might be a novel escape strategy used by the malaria liver stage.
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DOI：
10.1126/science.1227026
发表时间：
2012-11-23
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Choy A;Dancourt J;Mugo B;O'Connor TJ;Isberg RR;Melia TJ;Roy CR
通讯作者：
Roy CR
影响因子：
2.4
作者：
MEIS, JFGM;VERHAVE, JP;MEUWISSEN, JHET
通讯作者：
MEUWISSEN, JHET
Toll 样受体激动剂对约氏疟原虫肝期发育的抑制作用
影响因子：
2.2
作者：
Chen, J.;Xu, W.;Huang, F.
通讯作者：
Huang, F.
影响因子：
4.8
作者：
Noda, T;Ohsumi, Y
通讯作者：
Ohsumi, Y
影响因子：
4.4
作者：
Roland, Jacques;Soulard, Valerie;Pied, Sylviane
通讯作者：
Pied, Sylviane