Particulate β‐glucans synergistically activate TLR4 and Dectin‐1 in human dendritic cells

Scope The major receptor for β(1‐3)‐glucans on immune cells is considered to be Dectin‐1 receptor. Particulate β‐glucans induce stronger immune responses than soluble β‐glucans by clustering of Dectin‐1 receptors. Here, it was hypothesized that activation of other pattern recognition receptors such as Toll‐like receptor 4 (TLR4) can also contribute to enhanced activity of immune cells after exposure to particulate β‐glucans. Methods and results To test this hypothesis, reporter cell lines were designed expressing TLR4 with either Dectin‐1A or Dectin‐1B, that is, one of the two transcript variants of human Dectin‐1 receptors. Enhanced NF‐κB activation was observed after stimulation with particulate β‐glucans in both Dectin‐1A‐TLR4 and the Dectin‐1B‐TLR4 cell lines. This was different with soluble β‐glucans, which enhanced activation in Dectin‐1A‐TLR4 cell lines but not in Dectin‐1B‐TLR4 cells. The synergistic activation of TLR4 and Dectin‐1 by particulate β‐glucans was confirmed in human dendritic cells. The effects of particulate β‐glucan induced TLR4 binding were regulatory as blocking TLR4 enhanced pro‐inflammatory cytokine IL‐23, IL‐4, IL‐6, and TNF‐α production. Conclusion These results suggest that TLR4 and Dectin‐1 are synergistically activated by particulate β‐glucans, wherein TLR4 activates an immune regulatory pathway in human dendritic cells. Our data suggest that β‐glucan is an immune regulatory ligand for TLR4.