TLR4型
上睑下垂
脂多糖
细胞质
先天免疫系统
半胱氨酸蛋白酶1
胞浆
细胞生物学
免疫系统
启动(农业)
半胱氨酸蛋白酶8
细胞凋亡
生物
半胱氨酸蛋白酶
程序性细胞死亡
免疫学
信号转导
生物化学
酶
发芽
植物
作者
Jon A. Hagar,Daniel A. Powell,Youssef Aachoui,Robert K. Ernst,Edward A. Miao
出处
期刊:Science
[American Association for the Advancement of Science (AAAS)]
日期:2013-09-13
卷期号:341 (6151): 1250-1253
被引量:1016
标识
DOI:10.1126/science.1240988
摘要
Inflammatory caspases, such as caspase-1 and -11, mediate innate immune detection of pathogens. Caspase-11 induces pyroptosis, a form of programmed cell death, and specifically defends against bacterial pathogens that invade the cytosol. During endotoxemia, however, excessive caspase-11 activation causes shock. We report that contamination of the cytoplasm by lipopolysaccharide (LPS) is the signal that triggers caspase-11 activation in mice. Specifically, caspase-11 responds to penta- and hexa-acylated lipid A, whereas tetra-acylated lipid A is not detected, providing a mechanism of evasion for cytosol-invasive Francisella. Priming the caspase-11 pathway in vivo resulted in extreme sensitivity to subsequent LPS challenge in both wild-type and Tlr4-deficient mice, whereas Casp11-deficient mice were relatively resistant. Together, our data reveal a new pathway for detecting cytoplasmic LPS.
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