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

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  • Martijn H. den Brok

    (Radboud Institute for Molecular Life Sciences, Radboud UMC, Geert Grooteplein 26, 6525 GA
    Pain and Palliative Medicine, Radboud UMC, Geert Grooteplein 10)

  • Christian Büll

    (Radboud Institute for Molecular Life Sciences, Radboud UMC, Geert Grooteplein 26, 6525 GA)

  • Melissa Wassink

    (Radboud Institute for Molecular Life Sciences, Radboud UMC, Geert Grooteplein 26, 6525 GA)

  • Annemarie M. de Graaf

    (Radboud Institute for Molecular Life Sciences, Radboud UMC, Geert Grooteplein 26, 6525 GA)

  • Jori A. Wagenaars

    (Radboud Institute for Molecular Life Sciences, Radboud UMC, Geert Grooteplein 26, 6525 GA)

  • Marthe Minderman

    (Radboud Institute for Molecular Life Sciences, Radboud UMC, Geert Grooteplein 26, 6525 GA)

  • Mayank Thakur

    (Institute for Laboratory Medicine, Clinical Chemistry and Pathobiochemistry, Charité Universitätsmedizin, Augustenburger Platz 1, 13353)

  • Sebastian Amigorena

    (INSERM, Institut Curie, Section Recherche, Rue d'Ulm 26, 75005)

  • Eric O. Rijke

    (MSD Animal Health)

  • Carla C. Schrier

    (MSD Animal Health)

  • Gosse J. Adema

    (Radboud Institute for Molecular Life Sciences, Radboud UMC, Geert Grooteplein 26, 6525 GA)

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.

Suggested Citation

  • 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, 2016. "Saponin-based adjuvants induce cross-presentation in dendritic cells by intracellular lipid body formation," Nature Communications, Nature, vol. 7(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms13324
    DOI: 10.1038/ncomms13324
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    Cited by:

    1. Diego Calzada-Fraile & Salvador Iborra & Marta Ramírez-Huesca & Inmaculada Jorge & Enrico Dotta & Elena Hernández-García & Noa Martín-Cófreces & Estanislao Nistal-Villán & Esteban Veiga & Jesús Vázque, 2023. "Immune synapse formation promotes lipid peroxidation and MHC-I upregulation in licensed dendritic cells for efficient priming of CD8+ T cells," Nature Communications, Nature, vol. 14(1), pages 1-16, December.

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