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首页> 外文期刊>Infection and immunity >Activation of Dendritic Cells by Liposomes Prepared from Phosphatidylinositol Mannosides from Mycobacterium bovis Bacillus Calmette-Guérin and Adjuvant Activity In Vivo
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Activation of Dendritic Cells by Liposomes Prepared from Phosphatidylinositol Mannosides from Mycobacterium bovis Bacillus Calmette-Guérin and Adjuvant Activity In Vivo

机译：牛分枝杆菌卡介苗的磷脂酰肌醇甘露糖苷制备的脂质体对树突状细胞的活化及体内佐剂活性

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Liposome vesicles could be formed at 65°C from the chloroform-soluble, total polar lipids (TPL) extracted from Mycobacterium bovis bacillus Calmette-Guérin (BCG). Mice immunized with ovalbumin (OVA) entrapped in TPL liposomes produced both anti-OVA antibody and cytotoxic T lymphocyte responses. Murine bone marrow-derived dendritic cells were activated to secrete interleukin-6 (IL-6), IL-12, and tumor necrosis factor upon exposure to antigen-free TPL liposomes. Three phosphoglycolipids and three phospholipids comprising 96% of TPL were identified as phosphatidylinositol dimannoside, palmitoyl-phosphatidylinositol dimannoside, dipalmitoyl-phosphatidylinositol dimannoside, phosphatidylinositol, phosphatidylethanolamine, and cardiolipin. The activation of dendritic cells by liposomes prepared from each purified lipid component of TPL was evaluated in vitro. A basal activity of phosphatidylinositol liposomes to activate proinflammatory cytokine production appeared to be attributable to the tuberculosteric fatty acyl 19:0 chain characteristic of mycobacterial glycerolipids, as similar lipids lacking tuberculosteric chains showed little activity. Phosphatidylinositol dimannoside was identified as the primary lipid that activated dendritic cells to produce amounts of proinflammatory cytokines several times higher than the basal level, indicating the importance of mannose residues. Although the activity of phosphatidylinositol dimannoside was little influenced by palmitoylation of mannose at C-6, a further palmitoylation at inositol C-3 diminished the induction levels of IL-6 and IL-12. Further, OVA entrapped in palmitoyl-phosphatidylinositol dimannoside liposomes was delivered to dendritic cells for major histocompatibility complex class I presentation more effectively than TPL OVA-liposomes. BCG liposomes containing mannose lipids caused up-regulation of costimulatory molecules and CD40. Thus, the inclusion of pure phosphatidylinositol mannosides of BCG in lipid vesicle vaccines represents a simple and efficient option for targeting antigen delivery and providing immune stimulation.
机译：脂质体小泡可以在65°C下由从卡姆特-盖林（BCG）牛分枝杆菌中提取的，溶于氯仿的总极性脂质（TPL）形成。用包裹在TPL脂质体中的卵清蛋白（OVA）免疫的小鼠产生抗OVA抗体和细胞毒性T淋巴细胞反应。暴露于无抗原的TPL脂质体后，小鼠骨髓衍生的树突状细胞被激活以分泌白介素6（IL-6），IL-12和肿瘤坏死因子。鉴定出包含96％TPL的三种磷酸糖脂和三种磷脂为磷脂酰肌醇二甘露糖苷，棕榈酰磷脂酰肌醇二甘露糖苷，二棕榈酰磷脂酰肌醇二甘露糖苷，磷脂酰肌醇，磷脂酰乙醇胺和心磷脂。在体外评估由TPL的每种纯化脂质成分制备的脂质体对树突状细胞的激活。磷脂酰肌醇脂质体激活促炎性细胞因子产生的基础活性似乎归因于分枝杆菌甘油脂的结核性脂酰基19：0链特征，因为缺乏结核性链的相似脂质几乎没有活性。磷脂酰肌醇二甘露糖苷被鉴定为激活树突状细胞以产生比基础水平高几倍的促炎细胞因子数量的主要脂质，表明甘露糖残基的重要性。尽管磷脂酰肌醇二甘露糖苷的活性几乎不受甘露糖在C-6处的棕榈酰化的影响，但在肌醇C-3处进一步的棕榈酰化减少了IL-6和IL-12的诱导水平。此外，与TPL OVA-脂质体相比，包裹在棕榈酰基-磷脂酰肌醇二甘露糖苷脂质体中的OVA被更有效地递送至树突状细胞以用于主要的组织相容性复合物I类呈递。含有甘露糖脂质的BCG脂质体引起共刺激分子和CD40的上调。因此，在脂质囊泡疫苗中包含BCG的纯磷脂酰肌醇甘露糖苷代表靶向抗原递送和提供免疫刺激的简单有效的选择。

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