Vitamin D and Beta-Glucans Synergically Stimulate Human Macrophage Activity

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.

The Role of Vitamin D in Supporting Health in the COVID-19 Era

“…Moreover, it reduces the production of pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), INF-γ, interleukin (IL)-6, and IL-1, while increasing anti-inflammatory cytokines such as IL-10 [ 30 , 31 , 32 ]. In particular, a recent study focused on the synergic effect of calcitriol and beta-glucans, another well-known immunomodulator, on macrophage phagocytic activity and cytokines production; the authors concluded that both molecules converge on the same pathway and that the enhanced production of immunomodulatory cytokines observed after cotreatment with the two molecules was mediated by the increased vesicular acidification [ 33 ].…”

“…On the one hand, the NF-kB signaling pathway is partially blocked by active vitamin D [ 172 , 173 , 174 ]. On the other hand, ROS generated by the NF-kB signaling pathway are neutralized by the vitamin-D-dependent increased glutathione biosynthesis [ 33 , 175 ] and by the enhanced activity of various ROS-scavenging enzymes controlled by active vitamin D [ 163 ].…”

“…Moreover, the pH-dependent, altered lysosomal function of infected cells can result in perturbation of antigen presentation and in disruption of endolysosomal toll-like receptor signaling, which requires acidification, leading to altered immune responses. Active vitamin D can facilitate acidification through the transcriptional induction of vacuolar ATPase (V-ATPase), which is reported in osteoclasts and macrophages [ 33 , 186 ]; the effect on vesicle acidification counteracts the activity of ORF3a and decreases virus exit.…”

“…For example, other antioxidant molecules or ROS scavengers could be associated with vitamin D to enhance its antioxidant effects. Alternatively, limiting the use of drugs that are eliminated by conjugation with glutathione, thus, consuming antioxidant defenses, such as paracetamol, could reinforce the antioxidant effects of vitamin D. Furthermore, the acidification of the vesicles could be increased by the combination of vitamin D and beta-glucans, as recently demonstrated in vitro [ 33 ], which could hamper the viral escape from infected cell.…”

Efficiency of Resistant Starch and Dextrins as Prebiotics: A Review of the Existing Evidence and Clinical Trials

“…Prebiotics can furthermore aid the host's immune system in several ways: directly through immune cell stimulation (by β-glucans) or indirectly through the production of SCFA, which contributes to an increased activity of immune cells (T-helper cells, killer cells, and macrophages) [18][19][20]. Another indirect benefit is associated with competition between potentially pathogenic strains invading the gastrointestinal tract and beneficial species of bacteria (i.e., probiotics) [21].…”