Bacterial secretion system skews the fate of Legionella-containing vacuoles towards LC3-associated phagocytosis.
Bacterial secretion system skews the fate of Legionella-containing vacuoles towards LC3-associated phagocytosis.
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DOI：
10.1038/srep44795
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发表时间：
2017-03-20
影响因子：
4.6
通讯作者：
Nagai H
中科院分区：
文献类型：
--
作者：
Hubber A;Kubori T;Coban C;Matsuzawa T;Ogawa M;Kawabata T;Yoshimori T;Nagai H
内体-溶酶体成熟和大自噬的进化保守过程是限制细胞内细菌存活的既定机制。同样，另一种新出现的机制是LC 3相关吞噬作用（LAP）。在这里，我们报告说，细胞内空泡病原体，军团菌dumoffii，是专门针对的经典的内吞成熟和大自噬途径。感染后，大多数L. dumoffii存在于ER样空泡中，并在该小生境内复制，这涉及经典内体成熟的抑制。复制生态位的建立需要细菌的Dot/Icm IV型分泌系统（T4 SS）。有趣的是，L的剩余子集。dumoffii瞬时获得LC 3到L. Dot/Icm T4 SS依赖性方式的含dumoffii的空泡。LC 3修饰的空泡被一个明显未受损的单膜所束缚，并且不能与参与选择性自噬的分子（如泛素或衔接子）相关联。该过程需要toll样受体2、Rubicon、二酰基甘油信号传导和下游NADPH氧化酶，而ULK 1激酶是不稳定的。我们共同发现了一种细胞内病原体，其在感染细胞中的生存主要受到LAP的限制。结果表明L.杜莫氏菌是一种有价值的模式生物，用于研究特别是由细菌感染引起的腹泻的机制细节。
The evolutionarily conserved processes of endosome-lysosome maturation and macroautophagy are established mechanisms that limit survival of intracellular bacteria. Similarly, another emerging mechanism is LC3-associated phagocytosis (LAP). Here we report that an intracellular vacuolar pathogen, Legionella dumoffii, is specifically targeted by LAP over classical endocytic maturation and macroautophagy pathways. Upon infection, the majority of L. dumoffii resides in ER-like vacuoles and replicate within this niche, which involves inhibition of classical endosomal maturation. The establishment of the replicative niche requires the bacterial Dot/Icm type IV secretion system (T4SS). Intriguingly, the remaining subset of L. dumoffii transiently acquires LC3 to L. dumoffii-containing vacuoles in a Dot/Icm T4SS-dependent manner. The LC3-decorated vacuoles are bound by an apparently undamaged single membrane, and fail to associate with the molecules implicated in selective autophagy, such as ubiquitin or adaptors. The process requires toll-like receptor 2, Rubicon, diacylglycerol signaling and downstream NADPH oxidases, whereas ULK1 kinase is dispensable. Together, we have discovered an intracellular pathogen, the survival of which in infected cells is limited predominantly by LAP. The results suggest that L. dumoffii is a valuable model organism for examining the mechanistic details of LAP, particularly induced by bacterial infection.