Cytolysin-dependent delay of vacuole maturation in macrophages infected with Listeria monocytogenes
Cytolysin-dependent delay of vacuole maturation in macrophages infected with Listeria monocytogenes
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DOI：
10.1111/j.1462-5822.2005.00604.x
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发表时间：
2006-01-01
影响因子：
3.4
通讯作者：
Swanson, JA
中科院分区：
文献类型：
--
作者：
Henry, R;Shaughnessy, L;Swanson, JA
细菌病原菌单核细胞增生性李斯特氏菌通过溶细胞素LLO(LLO)的作用从空泡逃逸到胞浆，从而逃避巨噬细胞的抗菌机制。由于逃逸的时间和效率的异质性，有关LLO对LM液泡识别和运输的贡献的重要问题一直是无法解决的。蓝绿色荧光蛋白(CFP)标记的内细胞膜标记在巨噬细胞中的表达，以及黄色荧光蛋白(YFP)标记的LM进入由细菌裂解的细胞质的指示剂。LM从Rab5a阴性、溶酶体相关膜蛋白-1(LAMP1)阴性、Rab7阳性、磷脂酰肌醇3-磷酸[PI(3)P]阳性空泡中逃逸。Lm空泡不标记YFP-Rab5a，除非细菌首先用免疫球蛋白Ig G调理。与LLO缺乏的LM相比，野生型LM延迟了与LAMP1阳性溶酶体的液泡融合。细菌被阻止表达LLO，直到它们到达LAMP1阳性的溶酶体时才有效地逃逸。因此，LLO依赖的LM空泡与溶酶体融合的延迟为LM提供了相对于巨噬细胞防御的竞争优势，因为它为细菌提供了更多的时间在细胞器中穿透。
The bacterial pathogen Listeria monocytogenes (Lm) evades the antimicrobial mechanisms of macrophages by escaping from vacuoles to the cytosol, through the action of the cytolysin listeriolysin O (LLO). Because of heterogeneities in the timing and efficiency of escape, important questions about the contributions of LLO to Lm vacuole identity and trafficking have been inaccessible. Expression of cyan fluorescent protein (CFP)-labelled endocytic membrane markers in macrophages along with a yellow fluorescent protein (YFP)-labelled indicator of Lm entry to the cytosol identified compartments lysed by bacteria. Lm escaped from Rab5a-negative, lysosome-associated membrane protein-1 (LAMP1)-negative, Rab7-positive, phosphatidylinositol 3-phosphate [PI(3)P]-positive vacuoles. Lm vacuoles did not label with YFP-Rab5a unless the bacteria were first opsonized with IgG. Wild-type Lm delayed vacuole fusion with LAMP1-positive lysosomes, relative to LLO-deficient Lm. Bacteria prevented from expressing LLO until their arrival into LAMP1-positive lysosomes escaped inefficiently. Thus, the LLO-dependent delay of Lm vacuole fusion with lysosomes affords Lm a competitive edge against macrophage defences by providing bacteria more time in organelles they can penetrate.