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

Autor: Gosse J. Adema, Annemarie M.A. de Graaf, Marthe Minderman, Eric Onno Rijke, Mayank Thakur, Jori A. L. Wagenaars, Christian Büll, Melissa Wassink, Martijn H. den Brok, Schrier Carla Christina, Sebastian Amigorena
Rok vydání: 2016
Předmět:
0301 basic medicine
Cellular immunity
Skin Neoplasms
Inflammasomes
Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2]
medicine.medical_treatment
Melanoma
Experimental
General Physics and Astronomy
Lymphocyte Activation
Mice
Lipid droplet
Mice
Knockout
Antigen Presentation
Immunity
Cellular
CD11b Antigen
Multidisciplinary
Cross-presentation
Metabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6]
3. Good health
Cell biology
Tumour immunology
Female
Adjuvant
Proteasome Endopeptidase Complex
Science
Primary Cell Culture
Antigen presentation
Antigen-presenting cells
Biology
Cancer Vaccines
Article
General Biochemistry
Genetics and Molecular Biology
03 medical and health sciences
Cross-Priming
Adjuvants
Immunologic
Antigen
Cell Line
Tumor
medicine
Animals
Humans
Adjuvants
Antigen-presenting cell
Dendritic Cells
Lipid Droplets
General Chemistry
Saponins
Mice
Inbred C57BL
030104 developmental biology
Immunology
Cancer vaccine
Zdroj: Nature Communications, 7, 13324-13324
Nature Communications, Vol 7, Iss 1, Pp 1-14 (2016)
Nature Communications, 7, pp. 13324-13324
Nature Communications
ISSN: 2041-1723
Popis: 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.
Databáze: OpenAIRE
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