Dectin‐1 synergizes with TLR2 and TLR4 for cytokine production in human primary monocytes and macrophages

Summary The β‐glucan receptor dectin‐1 and Toll‐like receptors TLR2 and TLR4 are the main receptors for recognition of Candida albicans by the innate immune system. It has been reported that dectin‐1 amplifies TLR2‐dependent induction of cytokines in mouse models. In the present study we hypothesized that dectin‐1 has potent synergistic effects with both TLR2 and TLR4 in human PBMCs and macrophages. Human PBMCs and monocyte‐derived macrophages were stimulated with curdlan, a linear β‐1,3‐glucan‐polymer derived from Alcaligenes faecalis with specific ligand affinity for dectin‐1, in combination with the synthetic TLR2 ligand Pam3Cys and the ultrapure TLR4 ligand LPS. TNF‐α and IL‐10 production was measured in the supernatants with ELISA. Curdlan is a specific dectin‐1 ligand without TLR2‐ or TLR4‐stimulating properties. Human primary monocytes and macrophages express dectin‐1 on the cell membrane. Stimulation of human PBMCs with curdlan in combination with Pam3Cys or LPS leads to synergistic increase in TNF‐α production that was inhibited by GE2, a neutralizing dectin‐1 antibody. Dectin‐1‐dependent synergy between curdlan and TLR agonists was also apparent in human monocyte‐derived macrophages. Conclusively, dectin‐1 synergizes with both TLR2 and TLR4 pathways for the production of TNF‐α in human primary PBMCs and in monocyte‐derived macrophages.