Molecular mechanisms of inflammasome activation during microbial infections

被引:204
作者
Broz, Petr [1 ]
Monack, Denise M. [1 ]
机构
[1] Stanford Univ, Dept Microbiol & Immunol, Sch Med, Stanford, CA 94305 USA
关键词
inflammasome; Caspase-1; NLRs; ASC; Francisella tularensis; Salmonella typhimurium; INNATE IMMUNE-RESPONSE; LISTERIA-MONOCYTOGENES INFECTION; ENTERICA SEROVAR TYPHIMURIUM; CASPASE RECRUITMENT DOMAIN; BETA-CONVERTING ENZYME; ANTHRAX LETHAL TOXIN; III SECRETION SYSTEM; SPECK-LIKE PROTEIN; FACTOR-KAPPA-B; FRANCISELLA-TULARENSIS;
D O I
10.1111/j.1600-065X.2011.01041.x
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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-1 beta (IL-1 beta) 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 caspase-1 autoproteolysis and new insights into the structure of the inflammasome complex.
引用
收藏
页码:174 / 190
页数:17
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