Galectin-3, a marker for vacuole lysis by invasive pathogens
Galectin-3, a marker for vacuole lysis by invasive pathogens
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DOI：
10.1111/j.1462-5822.2009.01415.x
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发表时间：
2010-04-01
影响因子：
3.4
通讯作者：
Sansonetti, Philippe
中科院分区：
文献类型：
--
作者：
Paz, Irit;Sachse, Martin;Sansonetti, Philippe
志贺氏菌侵入巨噬细胞和上皮细胞，内化后溶解吞噬体并逃逸至细胞质。半乳糖凝集素-3是巨噬细胞和上皮细胞中丰富的蛋白质，属于β-半乳糖苷结合蛋白家族，半乳糖凝集素，在免疫应答、发育、分化、癌症和感染中具有许多功能。半乳糖凝集素作为胞质蛋白合成，并在非经典分泌后结合细胞外β-半乳糖苷。在这里，我们分析了志贺氏菌进入胞质溶胶后半乳糖凝集素-3的定位，并发现了一个惊人的现象。在细菌入侵后不久，细胞内半乳糖凝集素-3在内化细菌附近的结构中积累。通过使用免疫电子显微镜分析，我们确定了半乳糖凝集素-3在膜定位在吞噬体和小管和囊泡，来自内吞途径。我们还证明了半乳糖凝集素-3与宿主含N-乙酰基乳糖胺聚糖的结合是形成结构所需的。这些结构的积累是一个依赖于第三型分泌系统的过程。更具体地说，结构的存在严格依赖于吞噬空泡的溶解，也可以通过革兰氏阳性李斯特菌和沙门氏菌sifA突变体来显示。我们认为，含半乳糖凝集素-3的结构可以作为一个潜在的新工具，现场液泡溶解。
P>Shigella bacteria invade macrophages and epithelial cells and following internalization lyse the phagosome and escape to the cytoplasm. Galectin-3, an abundant protein in macrophages and epithelial cells, belongs to a family of beta-galactoside-binding proteins, the galectins, with many proposed functions in immune response, development, differentiation, cancer and infection. Galectins are synthesized as cytosolic proteins and following non-classical secretion bind extracellular beta-galactosides. Here we analysed the localization of galectin-3 following entry of Shigella into the cytosol and detected a striking phenomenon. Very shortly after bacterial invasion, intracellular galectin-3 accumulated in structures in vicinity to internalized bacteria. By using immuno-electron microscopy analysis we identified galectin-3 in membranes localized in the phagosome and in tubules and vesicles that derive from the endocytic pathway. We also demonstrated that the binding of galectin-3 to host N-acetyllactosamine-containing glycans, was required for forming the structures. Accumulation of the structures was a type three secretion system-dependent process. More specifically, existence of structures was strictly dependent upon lysis of the phagocytic vacuole and could be shown also by Gram-positive Listeria and Salmonella sifA mutant. We suggest that galectin-3-containing structures may serve as a potential novel tool to spot vacuole lysis.