Takeuchi O, Kawai T, Mühlradt P F, Morr M, Radolf J D, Zychlinsky A, Takeda K, Akira S
Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Suita, Japan.
Int Immunol. 2001 Jul;13(7):933-40. doi: 10.1093/intimm/13.7.933.
Bacterial lipoproteins (BLP) trigger immune responses via Toll-like receptor 2 (TLR2) and their immunostimulatory properties are attributed to the presence of a lipoylated N-terminus. Most BLP are triacylated at the N-terminus cysteine residue, but mycoplasmal macrophage-activating lipopeptide-2 kD (MALP-2) is only diacylated. Here we show that TLR6-deficient (TLR6(-/-)) cells are unresponsive to MALP-2 but retain their normal responses to lipopeptides of other bacterial origins. Reconstitution experiments in TLR2(-/-) TLR6(-/-) embryonic fibroblasts reveal that co-expression of TLR2 and TLR6 is absolutely required for MALP-2 responsiveness. Taken together, these results show that TLR6 recognizes MALP-2 cooperatively with TLR2, and appears to discriminate between the N-terminal lipoylated structures of MALP-2 and lipopeptides derived from other bacteria.
细菌脂蛋白(BLP)通过Toll样受体2(TLR2)触发免疫反应,其免疫刺激特性归因于脂酰化N端的存在。大多数BLP在N端半胱氨酸残基处被三酰化,但支原体巨噬细胞激活脂肽2 kD(MALP-2)仅被二酰化。在这里,我们表明TLR6缺陷(TLR6(-/-))细胞对MALP-2无反应,但对其他细菌来源的脂肽仍保持正常反应。在TLR2(-/-) TLR6(-/-)胚胎成纤维细胞中的重建实验表明,TLR2和TLR6的共表达是MALP-2反应性所绝对必需的。综上所述,这些结果表明TLR6与TLR2协同识别MALP-2,并且似乎能够区分MALP-2的N端脂酰化结构与其他细菌来源的脂肽。