HLH-30/TFEB-mediated autophagy functions in a cell-autonomous manner for epithelium intrinsic cellular defense against bacterial pore-forming toxin in C. elegans.
HLH-30/TFEB-mediated autophagy functions in a cell-autonomous manner for epithelium intrinsic cellular defense against bacterial pore-forming toxin in C. elegans.
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DOI：
10.1080/15548627.2016.1256933
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发表时间：
2017-02
期刊：
影响因子：
13.3
通讯作者：
Chen CS
中科院分区：
文献类型：
--
作者：
Chen HD;Kao CY;Liu BY;Huang SW;Kuo CJ;Ruan JW;Lin YH;Huang CR;Chen YH;Wang HD;Aroian RV;Chen CS
自噬是一种进化上保守的细胞内系统，通过降解和回收受损的细胞成分来维持细胞内稳态。据报道，转录因子HLH-30/TFEB介导的自噬调节对细菌感染的耐受性，但对激活HLH-30和自噬的真正细菌效应子知之甚少。在这里，我们揭示了细菌膜成孔毒素（PFT）以HLH-30依赖性方式诱导秀丽隐杆线虫的自噬。此外，自噬通过对PFT的异源性降解和PFT靶向肠细胞膜孔细胞的自主修复来控制动物对PFT毒性的易感性。优雅的这些结果表明，自噬途径和自噬诱导部分在转录水平上通过HLH-30激活，并需要保护后PFT中毒后生动物。总之，我们的数据显示了HLH-30介导的自噬和上皮细胞对体内细菌攻击的单一最常见模式的内在细胞防御之间的新的和强大的联系。
Autophagy is an evolutionarily conserved intracellular system that maintains cellular homeostasis by degrading and recycling damaged cellular components. The transcription factor HLH-30/TFEB-mediated autophagy has been reported to regulate tolerance to bacterial infection, but less is known about the bona fide bacterial effector that activates HLH-30 and autophagy. Here, we reveal that bacterial membrane pore-forming toxin (PFT) induces autophagy in an HLH-30-dependent manner in Caenorhabditis elegans. Moreover, autophagy controls the susceptibility of animals to PFT toxicity through xenophagic degradation of PFT and repair of membrane-pore cell-autonomously in the PFT-targeted intestinal cells in C. elegans. These results demonstrate that autophagic pathways and autophagy are induced partly at the transcriptional level through HLH-30 activation and are required to protect metazoan upon PFT intoxication. Together, our data show a new and powerful connection between HLH-30-mediated autophagy and epithelium intrinsic cellular defense against the single most common mode of bacterial attack in vivo.