Reduced Apoptosis of Mouse Macrophages Induced by yscW Mutant of Yersinia pestis Results from the Reduced Secretion of YopJ and Relates to Caspase‐3 Signal Pathway
Reduced Apoptosis of Mouse Macrophages Induced by yscW Mutant of Yersinia pestis Results from the Reduced Secretion of YopJ and Relates to Caspase‐3 Signal Pathway
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DOI：
10.1111/j.1365-3083.2009.02297.x
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发表时间：
2009-10
影响因子：
3.7
通讯作者：
Y. Bi;Z. Du;H. Yang;Z. Guo;Y. Tan;Z. Zhu;Ruifu Yang
中科院分区：
文献类型：
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作者：
Y. Bi;Z. Du;H. Yang;Z. Guo;Y. Tan;Z. Zhu;Ruifu Yang
致病性耶尔森氏菌的毒力取决于质粒编码的III型分泌系统（T3SS），该系统将6种耶尔森氏菌外蛋白（Yop）效应蛋白注入巨噬细胞的细胞质中，导致宿主防御机制的破坏。本文报道鼠疫耶尔森菌T3SS结构蛋白YscW参与了小鼠巨噬细胞凋亡的诱导。yscW突变株对小鼠腹腔和脾脏巨噬细胞以及RAW264.7细胞系的凋亡率均显著低于野生型（WT）鼠疫菌和yscW补充株。同时，巨噬细胞中凋亡诱导关键蛋白caspase‐3活性检测结果与WT、yscW突变株和互补株诱导巨噬细胞凋亡的变化一致，表明巨噬细胞凋亡与caspase‐3信号通路有关。然而，异位表达YscW在RAW264.7细胞中不能增加巨噬细胞的凋亡和死亡，提示YscW本身不能直接诱导巨噬细胞凋亡。为了深入了解这一现象的机制，我们分别研究了WT、突变株和互补株中YopJ的分泌情况，YopJ被认为是唯一与细胞凋亡相关的Yop效应物。结果表明，yscW突变株上清液中YopJ的分泌量明显低于WT或互补株。这意味着YscW虽然不直接诱导细胞凋亡，但可以通过减少YopJ的分泌间接影响细胞凋亡。
The virulence of the pathogenic Yersinia species depends on a plasmid‐encoded type III secretion system (T3SS) that injects six Yersinia outer protein (Yop) effector proteins into the cytosol of macrophages, leading to disruption of host defence mechanisms. Here, we report that a T3SS structural protein YscW of Yersinia pestis contributed to the induction of apoptosis of murine macrophages. The apoptotic percentage of macrophages, from both mouse peritoneal cavity and spleen, and of RAW264.7 cell line, caused by the yscW mutant strain was significantly lower than that by wild type (WT) Y. pestis and yscW complemented strain. Meanwhile, detection of caspase‐3 activity in macrophages, a key apoptosis‐inducing protein, showed coincident results with the changes of macrophage apoptosis induced by WT, yscW mutant and complemented strains, indicating that macrophage apoptosis was related to caspase‐3 signal pathways. However, ectopic expression of YscW in RAW264.7 cells cannot increase the macrophage apoptosis and death, suggesting that YscW itself could not induce macrophage apoptosis directly. To get insight into the mechanism of this phenomenon, we investigated the secretion of YopJ, which has been thought to be the only Yop effector related to apoptosis, in WT, mutant and complemented strains, respectively. Results showed that in yscW mutant strain, secretion of YopJ was decreased significantly in the supernatant than that in WT or complemented strain. This means although YscW does not induce apoptosis directly, it can indirectly affect apoptosis through reducing the secretion of YopJ.