Department of Biochemistry and Molecular Biology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
Exp Parasitol. 2011 Jul;128(3):205-11. doi: 10.1016/j.exppara.2011.03.010. Epub 2011 Mar 31.
The glycosylphosphatidylinositols (GPIs) of Plasmodium falciparum have been shown to activate macrophages and produce inflammatory responses. The activation of macrophages by malarial GPIs involves engagement of Toll like receptor 2 (TLR2) resulting in the intracellular signaling and production of cytokines. In the present study, we investigated the requirement of TLR1 and TLR6 for the TLR2 mediated cell signaling and proinflammatory cytokine production by macrophages. The data demonstrate that malarial GPIs, which contain three fatty acid substituents, preferentially engage TLR2-TLR1 dimeric pair than TLR2-TLR6, whereas their derivatives, sn-2 lyso GPIs, that contain two fatty acid substituents recognize TLR2-TLR6 with slightly higher selectivity as compared to TLR2-TLR1 heteromeric pair. These results are analogous to the recognition of triacylated bacterial and diacylated mycoplasmal lipoproteins, respectively, by TLR2-TLR1 and TLR2-TLR6 dimers, suggesting that the lipid portions of the microbial GPI ligands play essential role in determining their TLR recognition specificity.
疟原虫的糖基磷脂酰肌醇（GPIs）已被证明可以激活巨噬细胞并产生炎症反应。疟原虫 GPIs 激活巨噬细胞涉及 Toll 样受体 2（TLR2）的参与，导致细胞内信号转导和细胞因子的产生。在本研究中，我们研究了 TLR1 和 TLR6 对 TLR2 介导的巨噬细胞信号转导和促炎细胞因子产生的要求。数据表明，含有三个脂肪酸取代基的疟原虫 GPIs 优先与 TLR2-TLR1 二聚体结合，而不是 TLR2-TLR6，而其衍生物，sn-2 溶血 GPIs，含有两个脂肪酸取代基，与 TLR2-TLR6 的结合选择性略高于 TLR2-TLR1 异源二聚体。这些结果类似于 TLR2-TLR1 和 TLR2-TLR6 二聚体分别识别三酰化细菌和二酰化支原体脂蛋白，这表明微生物 GPI 配体的脂质部分在决定其 TLR 识别特异性方面起着重要作用。
