鼠伤寒沙门氏菌入侵蛋白SipB通过与半胱天冬酶-1结合诱导巨噬细胞凋亡。
The Salmonella invasin SipB induces macrophage apoptosis by binding to caspase-1.
作者信息
Hersh D, Monack D M, Smith M R, Ghori N, Falkow S, Zychlinsky A
机构信息
Skirball Institute, Department of Microbiology and Kaplan Cancer Center, New York University School of Medicine, 540 First Avenue, New York, NY 10016, USA.
出版信息
Proc Natl Acad Sci U S A. 1999 Mar 2;96(5):2396-401. doi: 10.1073/pnas.96.5.2396.
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-1beta. 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.
最近研究表明，沙门氏菌属可在受感染的巨噬细胞中诱导细胞凋亡。导致这一过程的机制尚不清楚。在本报告中，我们证实，Ⅲ型分泌系统的Inv-Spa靶标侵袭素SipB对于诱导细胞凋亡是必要且充分的。纯化的SipB显微注射到巨噬细胞中会导致细胞死亡。结合研究表明，SipB与促凋亡蛋白酶caspase-1相关联。这种相互作用导致caspase-1的激活，表现为其蛋白水解成熟及其底物白细胞介素-1β的加工。caspase-1活性对于细胞毒性至关重要。乙酰化的酪氨酸-缬氨酸-丙氨酸-天冬氨酸-氯甲基酮对caspase-1活性的功能抑制可阻断巨噬细胞的细胞毒性，而缺乏caspase-1的巨噬细胞对沙门氏菌诱导的细胞凋亡不敏感。综上所述，数据表明SipB的功能类似于志贺氏菌侵袭素IpaB。
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