Saponin-based adjuvants induce cross-presentation in dendritic cells by intracellular lipid body formation.
Saponin-based adjuvants induce cross-presentation in dendritic cells by intracellular lipid body formation.
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DOI：
10.1038/ncomms13324
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发表时间：
2016-11-07
影响因子：
16.6
通讯作者：
Adema, Gosse J.
中科院分区：
文献类型：
--
作者：
den Brok, Martijn H.;Bull, Christian;Wassink, Melissa;de Graaf, Annemarie M.;Wagenaars, Jori A.;Minderman, Marthe;Thakur, Mayank;Amigorena, Sebastian;Rijke, Eric O.;Schrier, Carla C.;Adema, Gosse J.
皂苷基佐剂（SBA）被用于动物和人类（癌症）疫苗，因为它们诱导保护性细胞免疫。它们的佐剂效力是炎性小体活化和增强树突状细胞（DC）的抗原交叉呈递的因素，但如何诱导抗原交叉呈递尚不清楚。在这里，我们表明，SBAs独特地诱导细胞内脂质体（LB）在CD11b+ DC亚群在体外和体内。在疫苗接种和原位肿瘤消融模型中使用遗传和药理学干扰，我们证明LB诱导与交叉呈递和T细胞活化中的皂苷依赖性增加有因果关系。这些发现将佐剂活性与LB形成联系起来，有助于SBA作为癌症疫苗组分的应用，并将刺激增强T细胞介导的免疫力的新佐剂的开发。 基于皂苷的佐剂正在被探索作为疫苗组分，因为它们诱导高水平的抗原交叉呈递，但其如何诱导尚不清楚。在这里，作者表明，这些佐剂通过驱动CD11b树突状细胞内脂质体的产生来增强交叉呈递。
Saponin-based adjuvants (SBAs) are being used in animal and human (cancer) vaccines, as they induce protective cellular immunity. Their adjuvant potency is a factor of inflammasome activation and enhanced antigen cross-presentation by dendritic cells (DCs), but how antigen cross-presentation is induced is not clear. Here we show that SBAs uniquely induce intracellular lipid bodies (LBs) in the CD11b+ DC subset in vitro and in vivo. Using genetic and pharmacological interference in models for vaccination and in situ tumour ablation, we demonstrate that LB induction is causally related to the saponin-dependent increase in cross-presentation and T-cell activation. These findings link adjuvant activity to LB formation, aid the application of SBAs as a cancer vaccine component, and will stimulate development of new adjuvants enhancing T-cell-mediated immunity. Saponin-based adjuvants are being explored as vaccine components as they induce high levels of antigen cross-presentation, but it is unknown how. Here the authors show that these adjuvants enhance cross-presentation by driving production of lipid bodies inside CD11b dendritic cells.
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DOI：
10.1084/jem.192.12.1685
发表时间：
2000-12-18
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
den Haan JM;Lehar SM;Bevan MJ
通讯作者：
Bevan MJ
影响因子：
4.2
作者：
Gilabert-Oriol, Roger;Thakur, Mayank;Weng, Alexander
通讯作者：
Weng, Alexander
影响因子：
15
作者：
Kim, Yong-Jae;Wang, Pengfei;Gin, David Y.
通讯作者：
Gin, David Y.
影响因子：
10.8
作者：
Cruz, Luis J.;Tacken, Paul J.;Figdor, Carl G.
通讯作者：
Figdor, Carl G.
影响因子：
32.4
作者：
Bougneres, Laurence;Helft, Julie;Tiwari, Sangeeta;Vargas, Pablo;Chang, Benny Hung-Junn;Chan, Lawrence;Campisi, Laura;Lauvau, Gregoire;Hugues, Stephanie;Kumar, Pradeep;Kamphorst, Alice O.;Dumenil, Ana-Maria Lennon;Nussenzweig, Michel;MacMicking, John D.;Amigorena, Sebastian;Guermonprez, Pierre
通讯作者：
Guermonprez, Pierre