Cutting edge:: a novel nonoxidative phagosomal mechanism exerted by cathepsin-D controls Listeria monocytogenes intracellular growth
Cutting edge:: a novel nonoxidative phagosomal mechanism exerted by cathepsin-D controls Listeria monocytogenes intracellular growth
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DOI：
10.4049/jimmunol.176.3.1321
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发表时间：
2006-02-01
影响因子：
4.4
通讯作者：
Alvarez-Dominguez, C
中科院分区：
文献类型：
--
作者：
del Cerro-Vadillo, E;Madrazo-Toca, F;Alvarez-Dominguez, C
解读李斯特菌。单核细胞增多症利用宿主细胞机制侵入哺乳动物细胞是了解这种食源性病原体发病机制的关键问题，这种食源性病原体可引起从胃肠炎到脑膜炎和流产的疾病。在这项研究中，我们表明，溶酶体乙酰胆碱-蛋白酶组织蛋白酶-D（Ctsd）是相当重要的非氧化性listericidal防御机制。我们观察到对L.与野生型相比，CTSD缺陷型小鼠中分离的成纤维细胞和骨髓巨噬细胞的单核细胞增多性感染和细菌的吞噬体内活力增加。这些发现得到了L. Ctsd缺陷小鼠感染后单核细胞增多症。在野生型细胞中瞬时转染Ctsd足以将这些野生型吞噬体恢复到杀微生物区室。基于突变菌感染实验、体外降解实验和免疫沉淀实验，我们认为组织蛋白酶D的主要作用靶点是主要毒力因子溶血素O。
Deciphering how Listeria. monocytogenes exploits the host cell machinery to invade mammalian cells is a key issue in understanding the pathogenesis of this food-borne pathogen, which can cause diseases ranging from gastroenteritis to meningitis and abortion. In this study, we show that the lysosomal aspartyl-protease cathepsin-D (Ctsd) is of considerable importance for nonoxidative listericidal defense mechanisms. We observed enhanced susceptibility to L. monocytogenes infection of fibroblasts and bone-marrow macrophages and increased intraphagosomal viability of bacteria in fibroblasts isolated from Ctsd-deficient mice compared with wild type. These findings are further supported by prolonged survival of L. monocytogenes in Ctsd-deficient mice after infection. Transient transfection of Ctsd in wild-type cells was sufficient to revert these wild-type phagosomes back to microbicidal compartments. Based on infection experiments with mutant bacteria, in vitro degradation, and immunoprecipitation experiments, we suggest that a major target of cathepsin D is the main virulence factor listeriolysin O.