Vitamin D and Beta-Glucans Synergically Stimulate Human Macrophage Activity

Int J Mol Sci. 2021 May 4;22(9):4869. doi: 10.3390/ijms22094869.

Abstract

Vitamin D and beta-glucans are both immunostimulants. Vitamin D exerts its beneficial effects on many components of the immune system. In macrophages, the hormone modulates both phagocytic activity and cytokine production; therefore, it plays an important role in mediating the innate immune response to infection. The immunomodulatory properties of beta-glucans are attributed to the ability of these fungal cell wall polysaccharides to bind to different receptors expressed on the cell surface of phagocytic and cytotoxic innate immune cells, including monocytes and macrophages. The intracellular signaling pathways activated by beta-glucans lead to enhanced phagocytosis and cytokine response. In this study we investigated the possible potentiation of immunomodulatory properties of the combined treatment with vitamin D and beta-glucans. The effects of 100 nM 1,25-dihydroxyvitamin D3 or 100 µg/mL beta-glucans were evaluated in human macrophages in terms of cytokine production, intracellular vesicle acidification and changes in energy metabolism, three hallmarks of macrophage antimicrobial activation. We found that all the analyzed parameters were enhanced by the co-treatment compared to the response to single molecules. The results of this study support the validity of a novel therapeutic approach that could boost the immune response, taking advantage of the synergy between two natural compounds.

Keywords: beta-glucans; human macrophage; immunostimulation; interleukin-8; mitochondrial metabolism; vacuolar ATPase; vesicle acidification; vitamin D.

MeSH terms

  • Adjuvants, Immunologic / pharmacology*
  • Calcitriol / pharmacology*
  • Cell Differentiation
  • Cell Line, Tumor
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / immunology
  • Drug Synergism
  • Gene Expression Regulation / drug effects*
  • Gene Expression Regulation / immunology
  • Humans
  • Interleukin-8 / genetics
  • Interleukin-8 / immunology
  • Macrophages / cytology
  • Macrophages / drug effects*
  • Macrophages / immunology
  • Mitochondria / drug effects
  • Mitochondria / immunology
  • Mitochondria / metabolism
  • Mitochondrial Proton-Translocating ATPases / genetics
  • Mitochondrial Proton-Translocating ATPases / immunology
  • Signal Transduction
  • THP-1 Cells
  • Vacuolar Proton-Translocating ATPases / genetics
  • Vacuolar Proton-Translocating ATPases / immunology
  • beta-Glucans / pharmacology*

Substances

  • Adjuvants, Immunologic
  • CXCL8 protein, human
  • Interleukin-8
  • MT-ATP6 protein, human
  • beta-Glucans
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Vacuolar Proton-Translocating ATPases
  • Mitochondrial Proton-Translocating ATPases
  • Calcitriol