The Salmonella invasin SipB induces macrophage apoptosis by binding to caspase-1
The Salmonella invasin SipB induces macrophage apoptosis by binding to caspase-1
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DOI：
10.1073/pnas.96.5.2396
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发表时间：
1999-03-02
影响因子：
11.1
通讯作者：
Zychlinsky, A
中科院分区：
文献类型：
--
作者：
Hersh, D;Monack, DM;Zychlinsky, A
最近，沙门氏菌属（Salmonella spp.）在感染的巨噬细胞中诱导凋亡。负责这一过程的机制尚不清楚。在这份报告中，我们建立了Inv-Spa III型分泌装置靶向侵袭素SipB是诱导细胞凋亡的必要和充分的。将纯化的SipB显微注射到巨噬细胞中导致细胞死亡。结合研究表明，SipB协会与促凋亡蛋白酶caspase-1。这种相互作用导致半胱天冬酶-1的活化，如在其蛋白水解成熟和其底物白细胞介素-1 β的加工中所见。Caspase-1活性对于细胞毒性是必不可少的。乙酰基-Tyr-Val-Ala-Asp-氯甲基酮对半胱天冬酶-1活性的功能性抑制阻断了巨噬细胞的细胞毒性，并且缺乏半胱天冬酶-1的巨噬细胞对沙门氏菌诱导的细胞凋亡不敏感。总之，数据表明SipB作为志贺氏菌侵袭素IpaB的类似物发挥作用。
Recently, Salmonella spp. were shown to induce apoptosis in infected macrophages. The mechanism responsible for this process is unknown. In this report, we establish that the Inv-Spa type III secretion apparatus target invasin SipB is necessary and sufficient for the induction of apoptosis. Purified SipB microinjected into macrophages led to cell death. Binding studies show that SipB associates with the proapoptotic protease caspase-1. This interaction results in the activation of caspase-1, as seen in its proteolytic maturation and the processing of its substrate interleukin-1 beta. Caspase-1 activity is essential for the cytotoxicity. Functional inhibition of caspase-1 activity by acetyl-Tyr-Val-Ala-Asp-chloromethyl ketone blocks macrophage cytotoxicity, and macrophages lacking caspase-1 are not susceptible to Salmonella-induced apoptosis. Taken together, the data demonstrate that SipB functions as an analog of the Shigella invasin IpaB.