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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adjuvants, Immunologic / chemistry
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Adjuvants, Immunologic / pharmacology
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Animals
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Antigen Presentation / drug effects
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Antigen Presentation / immunology
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CD11b Antigen / metabolism
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Cancer Vaccines / chemistry
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Cancer Vaccines / pharmacology*
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Cell Line, Tumor
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Cross-Priming / drug effects*
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Cross-Priming / immunology
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Dendritic Cells / immunology*
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Dendritic Cells / metabolism
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Female
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Humans
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Immunity, Cellular / drug effects
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Inflammasomes / immunology
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Lipid Droplets / drug effects
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Lipid Droplets / immunology
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Lymphocyte Activation / drug effects
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Lymphocyte Activation / immunology
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Melanoma, Experimental / immunology
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Melanoma, Experimental / therapy*
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Primary Cell Culture
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Proteasome Endopeptidase Complex / drug effects
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Proteasome Endopeptidase Complex / immunology
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Saponins / immunology
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Saponins / pharmacology*
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Skin Neoplasms / immunology
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Skin Neoplasms / therapy*
Substances
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Adjuvants, Immunologic
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CD11b Antigen
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Cancer Vaccines
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Inflammasomes
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Saponins
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Proteasome Endopeptidase Complex