Molecular mechanisms of inflammasome activation during microbial infections.
Molecular mechanisms of inflammasome activation during microbial infections.
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DOI：
10.1111/j.1600-065x.2011.01041.x
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发表时间：
2011-09
影响因子：
8.7
通讯作者：
Monack DM
中科院分区：
文献类型：
--
作者：
Broz P;Monack DM
先天免疫系统在快速识别和消除入侵微生物方面起着至关重要的作用。微生物的检测依赖于种系编码的模式识别受体（PRR），其识别必需的细菌分子，即所谓的病原体相关分子模式（PAMP）。属于NOD样受体（NLR）和PYHIN蛋白家族的PRR的子集检测宿主细胞的胞质溶胶中的病毒和细菌病原体，并诱导称为炎性体的多蛋白信号平台的组装。炎性小体作为哺乳动物半胱氨酸蛋白酶半胱天冬酶-1的活化平台，半胱天冬酶-1是先天免疫的中心介质。活性caspase-1促进白细胞介素-1 β（IL-1β）和IL-18以及参与细胞保护和组织修复的蛋白的成熟和释放。此外，caspase-1启动一种新的细胞死亡形式，称为细胞凋亡。在这里，我们讨论了两种模型细胞内病原体（土拉热弗朗西斯菌和鼠伤寒沙门氏菌）炎症体刺激的最新进展和我们的见解。最近对这些病原体的研究显著地塑造了我们对炎性小体激活的分子机制以及微生物如何逃避或操纵炎性小体活性的理解。此外，我们还回顾了炎性小体适配器ASC在caspase-1自蛋白水解中的作用，以及对炎性小体复合物结构的新认识。
The innate immune system plays a crucial role in the rapid recognition and elimination of invading microbes. Detection of microbes relies on germ-line encoded pattern recognition receptors (PRRs) that recognize essential bacterial molecules, so-called pathogen-associated molecular patterns (PAMPs). A subset of PRRs, belonging to the NOD-like receptor (NLR) and the PYHIN protein families, detects viral and bacterial pathogens in the cytosol of host cells and induces the assembly of a multi-protein signaling platform called the inflammasome. The inflammasome serves as an activation platform for the mammalian cysteine protease caspase-1, a central mediator of innate immunity. Active caspase-1 promotes the maturation and release of interleukin-1β (IL-1β) and IL-18 as well as protein involved in cytoprotection and tissue repair. In addition, caspase-1 initiates a novel form of cell death called pyroptosis. Here we discuss latest advances and our insights on inflammasome stimulation by two model intracellular pathogens, Francisella tularensis and Salmonella typhimurium. Recent studies on these pathogens have significantly shaped our understanding of the molecular mechanisms of inflammasome activation and how microbes can evade or manipulate inflammasome activity. In addition, we review the role of the inflammasome adapter ASC in the caspase-1 autoproteolysis and new insights into the structure of the inflammasome complex.