Autophagy is an immediate macrophage response to Legionella pneumophila
Autophagy is an immediate macrophage response to Legionella pneumophila
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DOI：
10.1111/j.1462-5822.2005.00509.x
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发表时间：
2005-06-01
影响因子：
3.4
通讯作者：
Swanson, MS
中科院分区：
文献类型：
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作者：
Amer, AO;Swanson, MS
被巨噬细胞吞噬后，嗜肺军团菌进入宽敞的空泡，迅速被内质网（ER）包裹，然后缓慢转移到溶酶体。在这里，我们证明了巨噬细胞自噬机制识别病原体吞噬体作为溶酶体运送的货物。自噬结合酶Atg7立即转移到含有毒性军团菌的吞噬体上。随后，第二种自噬酶at8和单丹酰尸胺（MDC），一种积聚在酸性自噬体中的染料，装饰病原体液泡。通过巨噬细胞对Atg8的加工和液泡的形成，依次获得Atg7、Atg8和MDC，可以判断自噬机制对IV型分泌能力强的军团菌释放到培养上清液中的10-30 kDa物质有反应。与雷帕霉素刺激的自噬体相比，军团菌液泡获得Atg7、Atg8和MDC的速度更慢，Atg8加工也延迟。此外，与允许军团菌的naip5突变体A/J巨噬细胞的自噬体相比，耐药的C57BL/6 J巨噬细胞成熟得更快，阻止了军团菌的有效复制。因此，我们讨论了巨噬细胞提升自噬作为感染屏障的模型，这一决定受到Naip蛋白和半胱天冬酶之间的调节相互作用的影响。
After ingestion by macrophages, Legionella pneumophila enter spacious vacuoles that are quickly enveloped by endoplasmic reticulum (ER), then slowly transferred to lysosomes. Here we demonstrate that the macrophage autophagy machinery recognizes the pathogen phagosome as cargo for lysosome delivery. The autophagy conjugation enzyme Atg7 immediately translocated to phagosomes harbouring virulent Legionella. Subsequently, Atg8, a second autophagy enzyme, and monodansyl-cadaverine (MDC), a dye that accumulates in acidic autophagosomes, decorated the pathogen vacuoles. The autophagy machinery responded to 10-30 kDa species released into culture supernatants by Type IV secretion-competent Legionella, as judged by the macrophages' processing of Atg8 and formation of vacuoles that sequentially acquired Atg7, Atg8 and MDC. When compared with autophagosomes stimulated by rapamycin, Legionella vacuoles acquired Atg7, Atg8 and MDC more slowly, and Atg8 processing was also delayed. Moreover, compared with autophagosomes of Legionella-permissive naip5 mutant A/J macrophages, those of resistant C57BL/6 J macrophages matured quickly, preventing efficient Legionella replication. Accordingly, we discuss a model in which macrophages elevate autophagy as a barrier to infection, a decision influenced by regulatory interactions between Naip proteins and caspases.