Binding of Toxoplasma gondii Glycosylphosphatidylinositols to Galectin-3 Is Required for Their Recognition by Macrophages
Binding of Toxoplasma gondii Glycosylphosphatidylinositols to Galectin-3 Is Required for Their Recognition by Macrophages
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DOI：
10.1074/jbc.m110.137588
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发表时间：
2010-10-22
影响因子：
4.8
通讯作者：
Schwarz, Ralph T.
中科院分区：
文献类型：
--
作者：
Debierre-Grockiego, Francoise;Niehus, Sebastian;Schwarz, Ralph T.
我们发现，巨噬细胞对弓形虫糖基磷脂酰肌醇（GPIs）的反应产生肿瘤坏死因子（TNF）α需要Toll样受体TLR 2和TLR 4的表达，但不需要其辅助受体CD 14。半乳糖凝集素-3是一种β-半乳糖苷结合蛋白，具有免疫调节作用，与TLR 2相关。我们用表面等离子体共振方法证明了T.弓形虫与人半乳糖凝集素-3以强亲和力和剂量依赖性方式结合。使用合成聚糖和从GPIs裂解的脂质部分表明，这两个部分都参与与半乳糖凝集素-3的相互作用。T的GPIs。弓形虫也与半乳糖凝集素-1结合，但亲和力较低，且仅通过脂质部分。在细胞水平，T.巨噬细胞中的弓形虫GPIs依赖于galectin-3的表达而不是galectin-1的表达。本研究首次鉴定了T. Galectin-3可能是巨噬细胞上呈递GPIs至TLR的共受体。
We showed that the production of tumor necrosis factor (TNF) alpha by macrophages in response to Toxoplasma gondii glycosylphosphatidylinositols (GPIs) requires the expression of both Toll-like receptors TLR2 and TLR4, but not of their coreceptor CD14. Galectin-3 is a beta-galactoside-binding protein with immune-regulatory effects, which associates with TLR2. We demonstrate here by using the surface plasmon resonance method that the GPIs of T. gondii bind to human galectin-3 with strong affinity and in a dose-dependent manner. The use of a synthetic glycan and of the lipid moiety cleaved from the GPIs shows that both parts are involved in the interaction with galectin-3. GPIs of T. gondii also bind to galectin-1 but with a lower affinity and only through the lipid moiety. At the cellular level, the production of TNF-alpha induced by T. gondii GPIs in macrophages depends on the expression of galectin-3 but not of galectin-1. This study is the first identification of a galectin-3 ligand of T. gondii origin, and galectin-3 might be a co-receptor presenting the GPIs to the TLRs on macrophages.