Saponin-based adjuvants induce cross-presentation in dendritic cells by intracellular lipid body formation.
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.
Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud UMC, Geert Grooteplein 26, 6525 GA Nijmegen, The Netherlands.|Department of Anesthesiology, Pain and Palliative Medicine, Radboud UMC, Geert Grooteplein 10, 6525 GA Nijmegen, The Netherlands.
Martijn H
0000-0002-2368-0411
MH
den Brok
Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud UMC, Geert Grooteplein 26, 6525 GA Nijmegen, The Netherlands.
Christian
C
Büll
Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud UMC, Geert Grooteplein 26, 6525 GA Nijmegen, The Netherlands.
Melissa
M
Wassink
Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud UMC, Geert Grooteplein 26, 6525 GA Nijmegen, The Netherlands.
Annemarie M
AM
de Graaf
Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud UMC, Geert Grooteplein 26, 6525 GA Nijmegen, The Netherlands.
Jori A
JA
Wagenaars
Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud UMC, Geert Grooteplein 26, 6525 GA Nijmegen, The Netherlands.
Marthe
M
Minderman
Institute for Laboratory Medicine, Clinical Chemistry and Pathobiochemistry, Charité Universitätsmedizin, Augustenburger Platz 1, 13353 Berlin, Germany.
Mayank
M
Thakur
INSERM, Institut Curie, Section Recherche, Rue d'Ulm 26, 75005 Paris, France.
Sebastian
S
Amigorena
MSD Animal Health, Wim de Korverstraat 35, 5831 AN Boxmeer, The Netherlands.
Eric O
EO
Rijke
MSD Animal Health, Wim de Korverstraat 35, 5831 AN Boxmeer, The Netherlands.
Carla C
CC
Schrier
Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud UMC, Geert Grooteplein 26, 6525 GA Nijmegen, The Netherlands.
Gosse J
GJ
Adema
D000276:Adjuvants, Immunologic / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects / Q000276:immunology; D039481:CD11b Antigen / Q000378:metabolism; D019496:Cancer Vaccines / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D045142:Cross-Priming / Q000187:drug effects* / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D058847:Inflammasomes / Q000276:immunology; D066292:Lipid Droplets / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008546:Melanoma, Experimental / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D061251:Primary Cell Culture; D046988:Proteasome Endopeptidase Complex / Q000187:drug effects / Q000276:immunology; D012503:Saponins / Q000276:immunology / Q000494:pharmacology*; D012878:Skin Neoplasms / Q000276:immunology / Q000628:therapy*
D000276:Adjuvants, Immunologic; D039481:CD11b Antigen; D019496:Cancer Vaccines; D058847:Inflammasomes; D012503:Saponins; D046988:Proteasome Endopeptidase Complex