Yersinia signals macrophages to undergo apoptosis and YopJ is necessary for this cell death
Yersinia signals macrophages to undergo apoptosis and YopJ is necessary for this cell death
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DOI：
10.1073/pnas.94.19.10385
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发表时间：
1997-09-16
影响因子：
11.1
通讯作者：
Falkow, S
中科院分区：
文献类型：
--
作者：
Monack, DM;Mecsas, J;Falkow, S
致病性耶尔森氏菌携带一个大的共同质粒，编码许多重要的毒力决定因子，包括耶尔森氏菌分泌的蛋白Yops，我们分析了野生型和突变型假结核耶尔森氏菌与巨噬细胞系RAW264.7和小鼠骨髓源性巨噬细胞相互作用的后果。野生型假结核杆菌在感染8小时后杀死约70%的感染RAW264.7巨噬细胞和骨髓源性巨噬细胞，我们发现假结核杆菌介导的细胞死亡是凋亡，不产生任何Yop蛋白的突变型假结核杆菌不再引起宿主细胞死亡。通过入侵蛋白或YadA附着在宿主细胞上是细胞死亡表型所必需的，一些Yop突变株不能表达一种或多种Yop蛋白，然后对其引起宿主细胞死亡的能力进行了工程设计，然后对其进行了表征。在YpkA Ser/Thr激酶中插入极性的突变株不表达YpkA或YopJ，不再能够引起细胞凋亡。不再产生YopE或YopH（一种酪氨酸磷酸酶）的突变体在巨噬细胞中诱导凋亡，与野生型相似。当yopJ以反式形式加入到ypkAyopJ突变体中时，该菌株在巨噬细胞中信号程序性细胞死亡的能力得以恢复，因此，yopJ是诱导凋亡所必需的。假结核杆菌在细胞培养中促进巨噬细胞凋亡的能力表明，这一过程对于在宿主中建立感染和逃避宿主免疫反应是重要的。
Pathogenic Yersinia spp. carry a large common plasmid that encodes a number of essential virulence determinants, Included in these factors are the Yersinia-secreted proteins called Yops, We analyzed the consequences of wild-type and mutant strains of Yersinia pseudotuberculosis interactions with the macrophage cell line RAW264.7 and murine bone marrow-derived macrophages. Wild-type Y. pseudotuberculosis kills approximate to 70% of infected RAW264.7 macrophages and marrow-derived macrophages after an 8-h infection, We show that the cell death mediated by Y. pseudotuberculosis is apoptosis, Mutant Y. pseudotuberculosis that do not make any Yop proteins no longer cause host cell death. Attachment to host cells via invasin or YadA is necessary for the cell death phenotype, Several Yop mutant strains that fail to express one or more Yop proteins were engineered and then characterized for their ability to cause host cell death, A mutant with a polar insertion in YpkA Ser/Thr kinase that does not express YpkA or YopJ is no longer able to cause apoptosis, In contrast, a mutant no longer making YopE or YopH (a tyrosine phosphatase) induces apoptosis in macrophages similar to wild type, When yopJ is added in trans to the ypkAyopJ mutant, the ability of this strain to signal programmed cell death in macrophages is restored, Thus, YopJ is necessary for inducing apoptosis. The ability of Y. pseudotuberculosis to promote apoptosis of macrophages in cell culture suggests that this process is important for the establishment of infection in the host and for evasion of the host immune response.