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

• Published in: Nature communications Vol. 7; no. 1; p. 13324
• Main Authors: den Brok, Martijn H., Büll, 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.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 07.11.2016; Nature Publishing Group; Nature Portfolio
• Subjects: 13/1; 13/31; 14/19; 14/28; 14/34; 14/35; 631/250/21/1293; 631/250/580; 631/250/590/2291; 64/110; 64/60; Ablation; Aluminum; Antigens; Cancer vaccines; Dendritic cells; Humanities and Social Sciences; Lipids; multidisciplinary; Proteins; Science; Science (multidisciplinary); Netherlands
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms13324

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.