陈嘉庚科学奖--生命科学奖  

Discoveries of cytosolic antibacterial immune receptors and their downstream pyroptosis executioner

作　　者：邵峰[1,2,3] Feng Shao(National Institute of Biological Sciences,Beijing 102206,China;Tsinghua Institute of Multidisciplinary Biomedical Research,Tsinghua University,Beijing 100084,China)

机构地区：[1]中国科学院 [2]北京生命科学研究所 [3]清华大学

出　　处：《科学通报》2022年第32期3766-3767,共2页Chinese Science Bulletin

摘　　要：获奖项目名称抗细菌天然免疫受体的发现及下游细胞焦亡机制获奖项目介绍首次鉴定了3个识别细菌主要模式分子的免疫受体/感知蛋白及其下游执行细胞焦亡的GSDMD蛋白,包括:(1)发现NAIP家族蛋白直接识别细菌鞭毛蛋白以及三型分泌系统结构蛋白,进而和另一NLR蛋白聚合形成炎症小体,通过活化caspase-1启动抗细菌炎症反应;(2)发现家族性地中海热自身炎症性疾病基因编码的Pyrin蛋白作为天然免疫模式识别受体。Shao's group for the first time identifies three cytosolic innate immune receptors or sensors for major bacterial molecular pattern molecules,as well as their downstream pyroptosis-execution protein.These include:(1)The NAIP family of NLR proteins functions as receptors to directly recognize bacterial flagellin and structural components in the toxin-injecting type II secretion system.NAIPs then co-oligomerize with another adaptor NLR protein NLRC4 to form the inflammasome complex,activate caspase-1 and initiates antibacterial immunity.(2)Pyrin,encoded by the familial Mediterranean fever(FMV)autoinflammatory disease gene MEFV,functions as an innate immune pattern-recognition receptor to detect inactivating-modifications of host Rho GTPases by several clinically important bacterial pathogens.Pyrin then also forms an inflammasome complex to activate caspase-1 and initiate antibacterial immunity.(3)Murine caspase-11 and human caspase-4/5 are intracellular receptors for bacterial LPS(endotoxin).LPS binding leads to oligomerization and activation of these inflammatory caspases,which play important roles in antibacterial immunity as well as septic shock.(4)Identify the novel gasdermin-D(GSDMD)protein,whose cleavage and activation by caspase-1,4,5,and 11 is the determinant for pyroptosis.The cleavage releases GSDMD N-terminal domain that directly executes pyroptotic cell death.(5)GSDMD represents a large gasdermin family of proteins that share the conserved N-terminal pore-forming domain and are all pyroptosis-execution proteins.Different family members respond to different signals and function in diverse functional contexts.This seminal discovery redefines the concept of pyroptosis and opens a new research area in inflammation and immunity.

关 键 词：细胞焦亡 家族性地中海热 模式识别受体 炎症小体 获奖项目 三型分泌系统 免疫受体 鞭毛蛋白 

分 类 号：R392[医药卫生—免疫学]