A novel caspase-1/toll-like receptor 4-independent pathway of cell death induced by cytosolic Shigella in infected macrophages
A novel caspase-1/toll-like receptor 4-independent pathway of cell death induced by cytosolic Shigella in infected macrophages
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DOI：
10.1074/jbc.m414671200
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发表时间：
2005-04-08
影响因子：
4.8
通讯作者：
Sasakawa, C
中科院分区：
文献类型：
--
作者：
Suzuki, T;Nakanishi, K;Sasakawa, C
志贺氏菌诱导巨噬细胞死亡是诱导急性炎症反应的重要一步，最终导致细菌性痢疾。先前报道的细胞死亡依赖于caspase-1与细胞内分泌的IPAB的相互作用，但在本研究中，我们发现志贺氏菌感染巨噬细胞也可以诱导细胞死亡，而不依赖于caspase-1或IPAB的活性。延时成像和电子显微镜分析表明，caspase-1依赖和非依赖的细胞死亡在形态上是难以区分的，两者都类似于坏死。对志贺氏菌突变株或大肠杆菌与李斯特菌混合感染的分析表明，革兰氏阴性菌的一个共同成分参与诱导caspase-1非依赖的细胞死亡。进一步的研究表明，细菌脂质A移位到巨噬细胞的胞浆中可能介导细胞死亡。值得注意的是，胞质细菌诱导的细胞死亡不依赖于TLR4。这些结果确定了由细胞内革兰氏阴性菌诱导的一种新的细胞死亡途径，该途径可能在微生物-宿主相互作用和炎症反应中发挥作用。
Shigella-induced macrophage cell death is an important step in the induction of acute inflammatory responses that ultimately lead to bacillary dysentery. Cell death was previously reported to be dependent upon the activation of caspase-1 via interaction with IpaB secreted by intracellular Shigella, but in this study, we show that Shigella infection of macrophages can also induce cell death independent of caspase-1 or IpaB activity. Time-lapse imaging and electron microscopic analyses indicated that caspase-1-dependent and -independent cell death is morphologically indistinguishable and that both resemble necrosis. Analyses of Shigella mutants or Escherichia coli using co-infection with Listeria suggested that a component common to Gram-negative bacteria is involved in inducing caspase-1-independent cell death. Further studies revealed that translocation of bacterial lipid A into the cytosol of macrophages potentially mediates cell death. Notably, cell death induced by cytosolic bacteria was TLR4-independent. These results identify a novel cell death pathway induced by intracellular Gram-negative bacteria that may play a role in microbial-host interactions and inflammatory responses.