GBP5 Promotes NLRP3 Inflammasome Assembly and Immunity in Mammals
GBP5 Promotes NLRP3 Inflammasome Assembly and Immunity in Mammals
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DOI：
10.1126/science.1217141
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发表时间：
2012-04-27
期刊：
影响因子：
56.9
通讯作者：
MacMicking, John D.
中科院分区：
文献类型：
--
作者：
Shenoy, Avinash R.;Wellington, David A.;MacMicking, John D.
炎症体是一种感觉复合体，它提醒免疫系统注意感染或组织损伤的存在。这些复合体组装NLR(核苷酸结合和寡聚，富含亮氨酸的重复序列)或ALR(黑色素瘤2样受体缺失)蛋白，激活caspase-1裂解和IL-1β/IL-18分泌。在这里，我们鉴定了一种刺激炎症小体组装的非NLR/ALR人类蛋白：鸟苷结合蛋白5(GBP5)。GBP5可促进NLRP3炎症体对病原菌和可溶性而非结晶型炎症体引发剂的选择性反应。GBP5(-/-)小鼠在体外表现出明显的caspase-1和IL-1β/IL-18裂解缺陷，在体内表现出宿主防御和依赖Nlrp3的炎症反应受损。因此，GBP5作为一种独特的变阻器用于激活NLRP3炎症体，并将我们对炎症体复合体的理解扩展到其核心机制之外。
Inflammasomes are sensory complexes that alert the immune system to the presence of infection or tissue damage. These complexes assemble NLR (nucleotide binding and oligomerization, leucine-rich repeat) or ALR (absent in melanoma 2-like receptor) proteins to activate caspase-1 cleavage and interleukin (IL)-1 beta/IL-18 secretion. Here, we identified a non-NLR/ALR human protein that stimulates inflammasome assembly: guanylate binding protein 5 (GBP5). GBP5 promoted selective NLRP3 inflammasome responses to pathogenic bacteria and soluble but not crystalline inflammasome priming agents. Generation of Gbp5(-/-) mice revealed pronounced caspase-1 and IL-1 beta/IL-18 cleavage defects in vitro and impaired host defense and Nlrp3-dependent inflammatory responses in vivo. Thus, GBP5 serves as a unique rheostat for NLRP3 inflammasome activation and extends our understanding of the inflammasome complex beyond its core machinery.