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

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

doi:10.1038/ncomms13324

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

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

48 Citations (Scopus)

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.

Original language	English
Article number	13324
Journal	Nature Communications
Volume	7
ISSN	2041-1723
DOIs	https://doi.org/10.1038/ncomms13324
Publication status	Published - 7 Nov 2016
Externally published	Yes

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title = "Saponin-based adjuvants induce cross-presentation in dendritic cells by intracellular lipid body formation",

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.",

author = "{den Brok}, {Martijn H} and Christian B{\"u}ll and Melissa Wassink and {de Graaf}, {Annemarie M} and Wagenaars, {Jori A} and Marthe Minderman and Mayank Thakur and Sebastian Amigorena and Rijke, {Eric O} and Schrier, {Carla C} and Adema, {Gosse J}",

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doi = "10.1038/ncomms13324",

language = "English",

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journal = "Nature Communications",

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T1 - Saponin-based adjuvants induce cross-presentation in dendritic cells by intracellular lipid body formation

AU - den Brok, Martijn H

AU - Büll, Christian

AU - Wassink, Melissa

AU - de Graaf, Annemarie M

AU - Wagenaars, Jori A

AU - Minderman, Marthe

AU - Thakur, Mayank

AU - Amigorena, Sebastian

AU - Rijke, Eric O

AU - Schrier, Carla C

AU - Adema, Gosse J

PY - 2016/11/7

Y1 - 2016/11/7

N2 - 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.

AB - 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.

U2 - 10.1038/ncomms13324

DO - 10.1038/ncomms13324

M3 - Journal article

C2 - 27819292

SN - 2041-1723

VL - 7

JO - Nature Communications

JF - Nature Communications

M1 - 13324

ER -

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

Abstract

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