Inflammatory caspases are innate immune receptors for intracellular LPS

doi:10.1038/nature13683

CORC > 北京大学 > 生命科学学院

	Inflammatory caspases are innate immune receptors for intracellular LPS
	Shi, Jianjin ; Zhao, Yue ; Wang, Yupeng ; Gao, Wenqing ; Ding, Jingjin ; Li, Peng ; Hu, Liyan ; Shao, Feng
刊名	nature
	2014
关键词	GRAM-NEGATIVE BACTERIA LIPOPOLYSACCHARIDE RECOGNITION CYTOPLASMIC LPS LIPID IVA ACTIVATION PROTEINS NLRP3 TLR4 MECHANISMS PYROPTOSIS
DOI	10.1038/nature13683
英文摘要	The murine caspase-11 non-canonical inflammasome responds to various bacterial infections. Caspase-11 activation-induced pyroptosis, in response to cytoplasmic lipopolysaccharide (LPS), is critical for endotoxic shock in mice. The mechanism underlying cytosolic LPS sensing and the responsible pattern recognition receptor are unknown. Here we show that human monocytes, epithelial cells and keratinocytes undergo necrosis upon cytoplasmic delivery of LPS. LPS-induced cytotoxicity was mediated by human caspase-4 that could functionally complement murine caspase-11. Human caspase-4 and the mouse homologue caspase-11 (hereafter referred to as caspase-4/11) and also human caspase-5, directly bound to LPS and lipid A with high specificity and affinity. LPS associated with endogenous caspase-11 in pyroptotic cells. Insect-cell purified caspase-4/11 underwent oligomerization upon LPS binding, resulting in activation of the caspases. Underacylated lipid IVa and lipopolysaccharide from Rhodobacter sphaeroides (LPS-RS) could bind to caspase-4/11 but failed to induce their oligomerization and activation. LPS binding was mediated by the CARD domain of the caspase. Binding-deficient CARD-domain point mutants did not respond to LPS with oligomerization or activation and failed to induce pyroptosis upon LPS electroporation or bacterial infections. The function of caspase-4/5/11 represents a new mode of pattern recognition in immunity and also an unprecedented means of caspase activation.; Multidisciplinary Sciences; SCI(E); PubMed; 53; ARTICLE; shaofeng@nibs.ac.cn; 7521; 187-+; 514
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/342022]
专题	生命科学学院
推荐引用方式 GB/T 7714	Shi, Jianjin,Zhao, Yue,Wang, Yupeng,et al. Inflammatory caspases are innate immune receptors for intracellular LPS[J]. nature,2014.
APA	Shi, Jianjin.,Zhao, Yue.,Wang, Yupeng.,Gao, Wenqing.,Ding, Jingjin.,...&Shao, Feng.(2014).Inflammatory caspases are innate immune receptors for intracellular LPS.nature.
MLA	Shi, Jianjin,et al."Inflammatory caspases are innate immune receptors for intracellular LPS".nature (2014).