AstragalusSaponins, Astragaloside VII and Newly Synthesized Derivatives, Induce Dendritic Cell Maturation and T Cell Activation Through IL-1β Production

AbstractAstragaloside VII (AST VII), a plant triterpenoid saponin isolated fromAstragalusspecies, shows promise as vaccine adjuvant, as it supports a balanced Th1/Th2 immune response. However, the underlying mechanisms of its adjuvant activity have not been defined. Here we investigated the impact of AST VII and its newly synthesized semi-synthetic analogs on human whole blood cells, as well as on mouse bone marrow-derived dendritic cells (BMDCs). Cells were stimulated with AST VII and its derivatives in the presence or absence of LPS or PMA/ionomycin and the secretion of cytokines and the expression of activation markers were analyzed by ELISA and flow cytometry, respectively. AST VII and its analogs increased the production of IL-1β in PMA/ionomycin stimulated human whole blood cells. In LPS-treated mouse BMDCs, AST VII increased the production of IL-1β and IL-12, and the expression of MHC II, CD86, and CD80. The strength of the IL-1β boost correlated directly with the hydrophobicity of the AST VII compounds. In mixed leukocyte reaction, AST VII and derivatives increased the expression of the activation marker CD44 on mouse CD4+and CD8+T cells. In conclusion, AST VII and its derivatives strengthen pro-inflammatory responses, support dendritic cell maturation, and T cell activationin vitro. Our results provide insights into the mechanisms of the adjuvant activities of AST VII and its analogs, which will be instrumental to improve their utility as vaccine adjuvant.