Streptococcus pneumoniae induces autophagy through the inhibition of the PI3K-I/Akt/mTOR pathway and ROS hypergeneration in A549 cells.
Streptococcus pneumoniae induces autophagy through the inhibition of the PI3K-I/Akt/mTOR pathway and ROS hypergeneration in A549 cells.
复制标题
肺炎链球菌通过抑制 A549 细胞中的 PI3K-I/Akt/mTOR 通路和 ROS 过度生成来诱导自噬
DOI：
10.1371/journal.pone.0122753
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Chen WX
中科院分区：
文献类型：
--
作者：
Li P;Shi J;He Q;Hu Q;Wang YY;Zhang LJ;Chan WT;Chen WX
本研究主要探讨了S. pneumoniae（Sp）诱导人肺泡上皮细胞自噬。SP是一种革兰氏阳性细胞外细菌，在A549细胞中激活自噬，并显著增加微管相关蛋白轻链3（LC 3）点。在SP感染的细胞中观察到典型的自噬体的积累和LC 3与磷脂酰乙醇胺的缀合作为自噬的指示。使用肺炎球菌溶血素（pneumolysin，pneumolysin）突变体，我们成功地证明了pneumolysin参与启动自噬，而不影响PI 3 K-III和Beclin 1的表达水平。PLY介导的自噬依赖于磷酸肌醇3-激酶/Akt/哺乳动物雷帕霉素靶蛋白（PI 3 K/Akt/mTOR）通路的抑制。此外，Sp还可导致A549细胞内活性氧（ROS）的大量产生。综上所述，Sp感染诱导的自噬是通过ROS过度生成和mTOR抑制由PLY介导的。PI 3 K-I和雷帕霉素（自噬诱导剂）增强细菌清除，而渥曼青霉素（自噬抑制剂）和乙酰半胱氨酸（ROS抑制剂）降低细胞内细菌清除。因此，Sp诱导的自噬代表了宿主保护机制，为呼吸道Sp感染的发病机制提供了新的见解。
The present study focused on the action mechanism of S. pneumoniae (Sp) in inducing autophagy in human alveolar epithelial cells. Sp, a gram-positive extracellular bacterium, activates autophagy with considerably increased microtuble-associated protein light chain 3 (LC3) punctation in A549 cells. The accumulation of typical autophagosomes and conjugation of LC3 to phosphatidylethanolamine were observed in Sp-infected cells as an indication of autophagy. Using the pneumolysin (PLY) mutant, we successfully demonstrated that PLY is involved in initiating autophagy without affecting the expression levels of PI3K-III and Beclin1. PLY-mediated autophagy depends on the inhibition of the phosphoinositide 3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway. Furthermore, Sp could also lead to the reactive oxygen species (ROS) hypergeneration in A549 cells. Taken together, Sp infection-induced autophagy is PLY-mediated through ROS hypergeneration and mTOR inhibition. PI3K-I and rapamycin (autophagy inducers) enhanced bacterial clearance, whereas wortmannin (autophagy inhibitor) and acetylcysteine (ROS inhibitor) reduced intracellular bacteria clearance. Thus, Sp-induced autophagy represents a host-protective mechanism, providing new insight into the pathogenesis of respiratory tract Sp infection.
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影响因子：
3.4
作者：
Mostowy S
通讯作者：
Mostowy S
影响因子：
3.1
作者：
BERRY, AM;YOTHER, J;PATON, JC
通讯作者：
PATON, JC
影响因子：
16
作者：
Kroemer G;Mariño G;Levine B
通讯作者：
Levine B
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：
5.7
作者：
Nair RR;Emmons MF;Cress AE;Argilagos RF;Lam K;Kerr WT;Wang HG;Dalton WS;Hazlehurst LA
通讯作者：
Hazlehurst LA