CD36 is a sensor of diacylglycerides
CD36 is a sensor of diacylglycerides
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DOI：
10.1038/nature03253
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发表时间：
2005-02-03
期刊：
影响因子：
64.8
通讯作者：
Beutler, B
中科院分区：
文献类型：
--
作者：
Hoebe, K;Georgel, P;Beutler, B
Toll样受体2（TLR 2）是识别细菌（1-8）、真菌（9，10）和原生动物（11）的许多分子组分所必需的。配体库的宽度似乎是不寻常的，即使人们认为TLR 2可能与TLR 1和6形成异聚体（参考文献12），并且可能有额外的蛋白质作为TLR 2活化的接头。在这里，我们表明，一个N-乙基-N-亚硝基脲诱导的无义突变的Cd 36（不经意）导致隐性免疫缺陷表型，其中巨噬细胞是不敏感的R-对映体的MALP-2（二酰化细菌脂肽）和脂磷壁酸。纯合子小鼠对金黄色葡萄球菌感染高度敏感。Cd 36（obl）巨噬细胞容易检测S-MALP-2、PAM（2）CSK（4）、PAM（3）CSK（4）和酵母聚糖，揭示了一些但不是所有的TLR 2配体依赖于CD 36。作为内源性分子的受体，CD 36也是微生物二酰甘油酯的选择性和非冗余传感器，通过TLR 2/6异源二聚体发出信号。
Toll-like receptor 2 (TLR2) is required for the recognition of numerous molecular components of bacteria(1-8), fungi(9,10) and protozoa(11). The breadth of the ligand repertoire seems unusual, even if one considers that TLR2 may form heteromers with TLRs 1 and 6 (ref. 12), and it is likely that additional proteins serve as adapters for TLR2 activation. Here we show that an N-ethyl-N-nitrosourea-induced nonsense mutation of Cd36 ( oblivious) causes a recessive immunodeficiency phenotype in which macrophages are insensitive to the R-enantiomer of MALP-2 ( a diacylated bacterial lipopeptide) and to lipoteichoic acid. Homozygous mice are hypersusceptible to Staphylococcus aureus infection. Cd36(obl) macrophages readily detect S-MALP-2, PAM(2)CSK(4), PAM(3)CSK(4) and zymosan, revealing that some - but not all TLR2 ligands are dependent on CD36. Already known as a receptor for endogenous molecules, CD36 is also a selective and nonredundant sensor of microbial diacylglycerides that signal via the TLR2/6 heterodimer.