Liposomal glycosphingolipids activate natural killer T cell-mediated immune responses through the endosomal pathway
Liposomal glycosphingolipids activate natural killer T cell-mediated immune responses through the endosomal pathway
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DOI：
10.1016/j.jconrel.2008.09.078
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发表时间：
2009-01-05
影响因子：
10.8
通讯作者：
Kumazawa, Yoshio
中科院分区：
文献类型：
--
作者：
Inoue, Joe;Ideue, Ryuichi;Kumazawa, Yoshio
自然杀伤T(NKT)细胞通过CD1d识别脂类抗原，如糖鞘糖脂(GSLS)，有助于宿主对各种病原体的防御。在这里，我们证明了从鞘氨醇单胞菌中分离出的GSLs并将其植入脂质体(GSL脂质体)中，可以增强NKT细胞和树突状细胞(DC)的激活。GSL脂质体在体外能显著促进脾细胞产生干扰素-γ，这种增强作用依赖于脂质体中对pH敏感的二油酰磷乙醇胺(DOPE)的含量。含有药物的GSL-脂质体在晚期内涵体中被明显破坏，这可能有助于GSLS有效地负载到CD1分子上。GSL脂质体治疗也激活了体内的NKT细胞和DC。综上所述，我们的结果有力地表明，GSL-脂质体可以有效地诱导NKT细胞介导的免疫反应，并可能作为一种免疫佐剂来诱导保护性免疫。(C)2008爱思唯尔B.V.保留所有权利。
Natural killer T (NKT) cells recognize lipid antigens, such as glycosphingolipids (GSLs), via CD1d and contribute to host defense against various pathogens. Here, we demonstrate that GSLs isolated from Sphingomonas bacteria and inserted into liposomes (GSL-liposomes) enhance the activation of NKT cells and dendritic cells (DCs). GSL-liposomes remarkably enhanced the production of IFN-gamma from splenocytes in vitro and this enhancement depended on the content of the pH-sensitive lipid dioleoyl-phosphoethanolamine (DOPE) in the liposomes. GSL-liposomes containing DOPE were clearly broken in late endosomes and this may facilitate effective loading of GSLs onto CD1 molecules. Treatment with GSL-liposomes also activated NKT cells and DCs in vivo. Collectively, our results strongly suggest that GSL-liposomes can effectively induce NKT cell-mediated immune responses and may be useful as an immune adjuvant for inducing protective immunity. (C) 2008 Elsevier B.V. All rights reserved.