The Myeloid LSECtin Is a DAP12-Coupled Receptor That Is Crucial for   Inflammatory Response Induced by Ebola Virus Glycoprotein

doi:10.1371/journal.ppat.1005487

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	The Myeloid LSECtin Is a DAP12-Coupled Receptor That Is Crucial for Inflammatory Response Induced by Ebola Virus Glycoprotein
	Zhao, Dianyuan ; Han, Xintao ; Zheng, Xuexing ; Wang, Hualei ; Yang, Zaopeng ; Liu, Di ; Han, Ke ; Liu, Jing ; Wang, Xiaowen ; Yang, Wenting ; Dong, Qingyang ; Yang, Songtao ; Xia, Xianzhu ; Tang, Li ; He, Fuchu
刊名	PLOS PATHOGENS
	2016
关键词	FLAGELLAR PROTEIN EXPORT N-TERMINAL REGION III SECRETION ESCHERICHIA-COLI SALMONELLA-TYPHIMURIUM EFFICIENT EXPORT AMILORIDE ANALOG CHAPERONE FLGN MOTIVE FORCE FLII ATPASE
DOI	10.1371/journal.ppat.1005487
英文摘要	Fatal Ebola virus infection is characterized by a systemic inflammatory response similar to septic shock. Ebola glycoprotein (GP) is involved in this process through activating dendritic cells (DCs) and macrophages. However, the mechanism is unclear. Here, we showed that LSECtin (also known as CLEC4G) plays an important role in GP-mediated inflammatory responses in human DCs. Anti-LSECtin mAb engagement induced TNF-alpha and IL-6 production in DCs, whereas silencing of LSECtin abrogated this effect. Intriguingly, as a pathogen-derived ligand, Ebola GP could trigger TNF-alpha and IL-6 release by DCs through LSECtin. Mechanistic investigations revealed that LSECtin initiated signaling via association with a 12-kDa DNAX-activating protein (DAP12) and induced Syk activation. Mutation of key tyrosines in the DAP12 immunoreceptor tyrosine-based activation motif abrogated LSECtin-mediated signaling. Furthermore, Syk inhibitors significantly reduced the GP-triggered cytokine production in DCs. Therefore, our results demonstrate that LSECtin is required for the GP-induced inflammatory response, providing new insights into the EBOV-mediated inflammatory response.; Chinese State Key Program in Basic Research [2012CB910203, 2013CB910802, 2013ZX10002009]; Beijing National Natural Science Foundation Projects [5142007]; State Key Laboratory of Proteomics [SKLP-Y201301]; SCI(E); ARTICLE; tangli08@aliyun.com; hefc@nic.bmi.ac.cn; 3; 12
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/492367]
专题	生命科学学院
推荐引用方式 GB/T 7714	Zhao, Dianyuan,Han, Xintao,Zheng, Xuexing,et al. The Myeloid LSECtin Is a DAP12-Coupled Receptor That Is Crucial for Inflammatory Response Induced by Ebola Virus Glycoprotein[J]. PLOS PATHOGENS,2016.
APA	Zhao, Dianyuan.,Han, Xintao.,Zheng, Xuexing.,Wang, Hualei.,Yang, Zaopeng.,...&He, Fuchu.(2016).The Myeloid LSECtin Is a DAP12-Coupled Receptor That Is Crucial for Inflammatory Response Induced by Ebola Virus Glycoprotein.PLOS PATHOGENS.
MLA	Zhao, Dianyuan,et al."The Myeloid LSECtin Is a DAP12-Coupled Receptor That Is Crucial for Inflammatory Response Induced by Ebola Virus Glycoprotein".PLOS PATHOGENS (2016).