Innate immune sensing of bacterial modifications of Rho GTPases by the   Pyrin inflammasome

doi:10.1038/nature13449

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	Innate immune sensing of bacterial modifications of Rho GTPases by the Pyrin inflammasome
	Xu, Hao ; Yang, Jieling ; Gao, Wenqing ; Li, Lin ; Li, Peng ; Zhang, Li ; Gong, Yi-Nan ; Peng, Xiaolan ; Xi, Jianzhong Jeff ; Chen, She ; Wang, Fengchao ; Shao, Feng
刊名	nature
	2014
关键词	FAMILIAL MEDITERRANEAN FEVER GTP-BINDING PROTEINS CLOSTRIDIUM-DIFFICILE BURKHOLDERIA-CENOCEPACIA TOXIN-B ACTIN CYTOSKELETON VIBRIO-CHOLERAE RTX TOXIN ACTIVATION SYSTEM
DOI	10.1038/nature13449
英文摘要	Cytosolic inflammasome complexes mediated by a pattern recognition receptor (PRR) defend against pathogen infection by activating caspase 1. Pyrin, a candidate PRR, can bind to the inflammasome adaptor ASC to form a caspase 1-activating complex(1,2). Mutations in the Pyrin-encoding gene, MEFV, cause a human autoinflammatory disease known as familial Mediterranean fever(3-5). Despite important roles in immunity and disease, the physiological function of Pyrin remains unknown. Here we show that Pyrin mediates caspase 1 inflammasome activation in response to Rho-glucosylation activity of cytotoxin TcdB(6-8), a major virulence factor of Clostridium difficile, which causes most cases of nosocomial diarrhoea. The glucosyltransferase-inactive TcdB mutant loses the inflammasome-stimulating activity. Other Rho-inactivating toxins, including FIC-domain adenylyltransferases (Vibrioparahaemolyticus VopS and Histophilus somnilbpA) and Clostridium botulinum ADP-ribosylating C3 toxin, can also biochemically activate the Pyrin inflammasome in their enzymatic activitydependent manner. These toxins all target the Rho subfamily and modify a switch-I residue. We further demonstrate that Burkholderia cenocepacia inactivates RHOA by deamidating Asn 41, also in the switch-I region, and thereby triggers Pyrin inflammasome activation, both of which require the bacterial type VI secretion system (T6SS). Loss of the Pyrin inflammasome causes elevated intra-macrophage growth of B. cenocepacia and diminished lung inflammation in mice. Thus, Pyrin functions to sense pathogen modification and inactivation of Rho GTPases, representing a new paradigm in mammalian innate immunity.; Multidisciplinary Sciences; SCI(E); PubMed; 33; ARTICLE; shaofeng@nibs.ac.cn; 7517; 237-+; 513
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/342126]
专题	工学院
推荐引用方式 GB/T 7714	Xu, Hao,Yang, Jieling,Gao, Wenqing,et al. Innate immune sensing of bacterial modifications of Rho GTPases by the Pyrin inflammasome[J]. nature,2014.
APA	Xu, Hao.,Yang, Jieling.,Gao, Wenqing.,Li, Lin.,Li, Peng.,...&Shao, Feng.(2014).Innate immune sensing of bacterial modifications of Rho GTPases by the Pyrin inflammasome.nature.
MLA	Xu, Hao,et al."Innate immune sensing of bacterial modifications of Rho GTPases by the Pyrin inflammasome".nature (2014).