Saponin-based adjuvants induce cross-presentation in dendritic cells by intracellular lipid body formation

皂苷类佐剂通过细胞内脂质体的形成诱导树突状细胞的交叉呈递

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作者:Martijn H den Brok, Christian Büll, Melissa Wassink, Annemarie M de Graaf, Jori A Wagenaars, Marthe Minderman, Mayank Thakur, Sebastian Amigorena, Eric O Rijke, Carla C Schrier, Gosse J Adema

Abstract

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.

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