Adjuvant-active aqueous extracts from Artemisia rupestris L. improve immune responses through TLR4 signaling pathway

Vaccine. 2017 Feb 15;35(7):1037-1045. doi: 10.1016/j.vaccine.2017.01.002. Epub 2017 Jan 19.

Abstract

Activating innate immunity by an adjuvant is required in vaccine development. The study aims to investigate adjuvant effects of aqueous extracts of Artemisia rupestris L. (AEAR) in vivo and in vitro. ICR mice were subcutaneously administered with antigen and AEAR at various doses to evaluate their immune responses of antibodies, dendritic cells (DCs), regulatory T cells (Treg), splenic lymphocyte, and cytokine. The evaluation results showed that AEAR could largely increase titers of antigen-specific antibodies (IgG, IgG1, and IgG2a) and T cell proliferation. AEAR also increased expression of IFN-γ in CD8+T cells as well as IL-4 and INF-γ expression in CD4+T cells. Expression levels of MHC-II, CD40, CD80, and CD86 on DCs were significantly elevated, whereas the Treg frequency was significantly decreased. AEAR (200μg) showed remarkable adjuvant activity. Furthermore, AEAR enhanced MHC-II, CD40, CD80, and CD86 expression as well as the yields of TNF-α and IL-12 on DCs through toll-like receptor4 (TLR4) in vitro. Those results indicated that AEAR could serve as an efficacious immune stimulator for vaccines because it significantly enhanced specific immune responses by promoting DCs maturation and reduced Treg through TLR4 signaling pathway.

Keywords: Adjuvant effect; Aqueous extract; Artemisia rupestris L.; Dendritic cells; TLR4.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / pharmacology*
  • Animals
  • Antigens, CD / genetics
  • Antigens, CD / immunology
  • Artemisia / chemistry*
  • Dendritic Cells / cytology
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology
  • Female
  • Gene Expression Regulation
  • Histocompatibility Antigens Class II / genetics
  • Histocompatibility Antigens Class II / immunology
  • Immunoglobulin G / biosynthesis
  • Interferon-gamma / genetics
  • Interferon-gamma / immunology
  • Interleukin-12 / genetics
  • Interleukin-12 / immunology
  • Interleukin-4 / genetics
  • Interleukin-4 / immunology
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred ICR
  • Ovalbumin / administration & dosage
  • Ovalbumin / immunology*
  • Plant Extracts / chemistry
  • Signal Transduction / drug effects*
  • Spleen / cytology
  • Spleen / drug effects
  • Spleen / immunology
  • T-Lymphocytes, Regulatory / cytology
  • T-Lymphocytes, Regulatory / drug effects*
  • T-Lymphocytes, Regulatory / immunology
  • Toll-Like Receptor 4 / genetics
  • Toll-Like Receptor 4 / immunology*
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • Adjuvants, Immunologic
  • Antigens, CD
  • Histocompatibility Antigens Class II
  • Immunoglobulin G
  • Plant Extracts
  • Tlr4 protein, mouse
  • Toll-Like Receptor 4
  • Tumor Necrosis Factor-alpha
  • Interleukin-12
  • Interleukin-4
  • Interferon-gamma
  • Ovalbumin