Abstract
Dendritic cells (DCs) are powerful antigen-presenting cells that are often used to evaluate adjuvants, particularly for adjuvant selection for various vaccines. Here, polysaccharides (named ALP) isolated from leaves of Annona muricata L., which are used in traditional medicine such as for bacterial infections and inflammatory diseases, were evaluated as an adjuvant candidate that can induce anti-tumor activity. We first confirmed the phenotypic (surface molecules, cytokines, antigen uptake, and antigen-presenting ability) and functional alterations (T cell proliferation/activation) of DCs in vitro. We also confirmed the adjuvant effect by evaluating anti-tumor activity and immunity using an ALP-treated DC-immunized mouse model. ALP functionally induced DC maturation by up-regulating the secretion of Th1-polarizing pro-inflammatory cytokines, the expression of surface molecules, and antigen-presenting ability. ALP triggered DC maturation, which is dependent on the activation of the MAPK and NF-κB signaling pathways. ALP-activated DCs showed an ample capacity to differentiate naive T cells to Th1 and activated CD8+ T cells effectively. The systemic administration of DCs that pulse ALP and ovalbumin peptides strongly increased cytotoxic T lymphocyte (CTL) activity (by 9.5% compared to that in the control vaccine groups), the generation of CD107a-producing multifunctional T cells, and Th1-mediated humoral immunity, and caused a significant reduction (increased protection by 29% over that in control vaccine groups) in tumor growth. ALP, which triggers the Th1 and CTL response, provides a basis for a new adjuvant for various vaccines.
Highlights
Vaccines are a safe and effective way to treat, mitigate and prevent various diseases such as glioblastoma, melanoma cancer, tuberculosis, and hepatitis infection, and they help the body’s immune system to recognize and combat specific harmful diseases [1,2,3]
Matured Dendritic cells (DCs) can induce the increased expression of cytokines and surface molecules involved in T cell activation and the activation of antigen-presenting ability with reduced antigen uptake [25]
Based on the characteristic of DCs, we examined whether A. muricata L. leaf polysaccharide (ALP) could induce DC maturation
Summary
Vaccines are a safe and effective way to treat, mitigate and prevent various diseases such as glioblastoma, melanoma cancer, tuberculosis, and hepatitis infection, and they help the body’s immune system to recognize and combat specific harmful diseases [1,2,3]. Nutrients 2020, 12, 1602 candidates have a reduced capacity to induce strong innate and adaptive immune responses [6,7,8]. These vaccines can induce a robust immune response when used with adjuvants that can enhance the immune response [8,9]. In this regard, several studies are underway to enhance and improve the immunogenicity of vaccines by using various adjuvants, and many researchers have focused on the development of an effective adjuvant as a disease-target immune enhancer [10,11]
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