These two authors contributed equally to the study.
Dectin-1 synergizes with TLR2 and TLR4 for cytokine production in human primary monocytes and macrophages
Article first published online: 28 JUN 2008
© 2008 The Authors. Journal compilation © 2008 Blackwell Publishing Ltd
Volume 10, Issue 10, pages 2058–2066, October 2008
How to Cite
Ferwerda, G., Meyer-Wentrup, F., Kullberg, B.-J., Netea, M. G. and Adema, G. J. (2008), Dectin-1 synergizes with TLR2 and TLR4 for cytokine production in human primary monocytes and macrophages. Cellular Microbiology, 10: 2058–2066. doi: 10.1111/j.1462-5822.2008.01188.x
- Issue published online: 8 SEP 2008
- Article first published online: 28 JUN 2008
- Received 6 March, 2008; revised 1 June, 2008; accepted 2 June, 2008.
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.