Leishmania lipophosphoglycan (LPG) activates NK cells through toll-like receptor-2
Leishmania lipophosphoglycan (LPG) activates NK cells through toll-like receptor-2
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DOI：
10.1016/s0166-6851(03)00160-9
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发表时间：
2003-08-31
影响因子：
1.5
通讯作者：
Isibasi, A
中科院分区：
文献类型：
--
作者：
Becker, I;Salaiza, N;Isibasi, A
Toll样受体（TLR）介导细胞对微生物共有的保守分子模式的应答。我们报告说，TLR-2对人类NK细胞的上调和刺激利什曼原虫主要脂磷酸聚糖（LPG），磷酸聚糖属于一个家庭的独特利什曼原虫糖缀合物。我们发现纯化的L.主要LPG上调NK细胞中TLR-2的mRNA和膜表达。此外，IFN-γ和TNF-α的产生和NF-κ B的核转位增强。激活效果更强烈的液化石油气纯化感染性后循环寄生虫比非感染性前循环利什曼原虫。由于来自寄生虫生长周期的这两个阶段的分子之间的差异完全在于磷酸糖重复结构域的数量和这些结构域的分支的聚糖侧链的组成，我们建议TLR-2可能区分磷酸化的聚糖重复LPG分子。LPG对细胞因子产生和对TLR-2的膜表达的影响可以用抗LPG的mAb的F（ab '）2片段阻断（WIC 79.3）。共聚焦显微镜显示LPG和TLR-2在NK细胞膜上共定位。通过用抗TLR-2和抗LPG mAb进行免疫沉淀，然后分别用抗LPG和抗TLR-2进行免疫印迹，证明LPG与NK细胞中TLR-2的结合。两种抗体都识别免疫复合物。这些结果表明，NK细胞能够识别，并激活，利什曼原虫LPG通过TLR-2，使他们能够自主参与先天免疫系统，从而增加了有效的破坏寄生虫。(C)2003 Elsevier B. V.保留所有权利。
Toll-like receptors (TLRs) mediate the cellular response to conserved molecular patterns shared by microorganisms. We report that TLR-2 on human NK cells is upregulated and stimulated by Leishmania major lipophosphoglycan (LPG), a phosphoglycan belonging to a family of unique Leishmania glycoconjugates. We found that purified L. major LPG upregulates both mRNA and the membrane expression of TLR-2 in NK cells. Additionally, IFN-gamma and TNF-alpha production and nuclear translocation of NF-kappaB was enhanced. The activation effect was more intense with LPG purified from infectious metacyclic parasites than from noninfectious procyclic Leishmania. Since the difference between the molecules derived from these two stages of the parasite growth cycle lies exclusively in the number of phosphosaccharide repeat domains and in the composition of glycan side chains that branch off these domains, we propose that TLR-2 possibly distinguishes between phosphorylated glycan repeats on LPG molecules. The effect of LPG on cytokine production and on membrane expression of TLR-2 could be blocked with F(ab')2 fragments of the mAb against LPG (WIC 79.3). Confocal microscopy demonstrated the co-localization of LPG and TLR-2 on the NK cell membrane. Binding of LPG to TLR-2 in NK cells was demonstrated by immunoprecipitations done with anti-TLR-2 and anti-LPG mAb followed by immunoblotting with anti-LPG and anti-TLR-2, respectively. Both antibodies recognized the immune complexes. These results suggest that NK cells are capable of recognition of, and activation by, Leishmania LPG through TLR-2, enabling them to participate autonomously in the innate immune system and thereby increasing the effective destruction of the parasite. (C) 2003 Elsevier B.V. All rights reserved.