Galectin-3 directs antimicrobial guanylate binding proteins to vacuoles furnished with bacterial secretion systems
Galectin-3 directs antimicrobial guanylate binding proteins to vacuoles furnished with bacterial secretion systems
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DOI：
10.1073/pnas.1615771114
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发表时间：
2017-02-28
影响因子：
11.1
通讯作者：
Coers, Joern
中科院分区：
文献类型：
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作者：
Feeley, Eric M.;Pilla-Moffett, Danielle M.;Coers, Joern
许多侵入性细菌建立含病原体液泡（pv）作为微生物生长的细胞内壁龛。对这些感染的免疫依赖于宿主细胞识别pv作为宿主防御目标的能力。几种宿主防御蛋白向pv的传递是由ifn诱导的鸟苷酸结合蛋白（GBPs）控制的，这些蛋白本身通过不明确的机制与pv对接。在这里，我们证明了GBPs检测细菌蛋白分泌系统作为与pv相关的“发病模式”的存在。我们报道了GBP2向含军团菌液泡的传递依赖于细菌Dot/Icm分泌系统，而GBP2向含耶尔森菌液泡（YCVs）的传递需要高分泌耶尔森菌转座蛋白。我们发现，细菌分泌系统的存在将胞质碳水化合物结合蛋白半乳糖凝集素-3引导到pv，并且在半乳糖凝集素-3缺乏的细胞中，GBP1和GBP2向含有军团菌的液泡或ycv的传递大大减少。我们的研究结果表明，细菌分泌系统插入PV膜刺激半乳糖凝集素-3依赖性抗菌GBPs向PV募集，作为协调宿主防御程序的一部分。
Many invasive bacteria establish pathogen-containing vacuoles (PVs) as intracellular niches for microbial growth. Immunity to these infections is dependent on the ability of host cells to recognize PVs as targets for host defense. The delivery of several host defense proteins to PVs is controlled by IFN-inducible guanylate binding proteins (GBPs), which themselves dock to PVs through poorly characterized mechanisms. Here, we demonstrate that GBPs detect the presence of bacterial protein secretion systems as "patterns of pathogenesis" associated with PVs. We report that the delivery of GBP2 to Legionella-containing vacuoles is dependent on the bacterial Dot/Icm secretion system, whereas the delivery of GBP2 to Yersiniacontaining vacuoles (YCVs) requires hypersecretion of Yersinia translocon proteins. We show that the presence of bacterial secretion systems directs cytosolic carbohydrate-binding protein Galectin-3 to PVs and that the delivery of GBP1 and GBP2 to Legionella-containing vacuoles or YCVs is substantially diminished in Galectin-3-deficient cells. Our results illustrate that insertion of bacterial secretion systems into PV membranes stimulates Galectin-3-dependent recruitment of antimicrobial GBPs to PVs as part of a coordinated host defense program.