Immune effects of β-glucan are determined by combined effects on Dectin-1, TLR2, 4 and 5

- Particulate β-glucans is a stronger Dectin-1 activator than soluble β-glucan.
- Dectin-1 stimulated THP-1 macrophages TLR2 and TLR4 activate an immune regulatory pathway while TLR5-blockade was inactive.
- β-glucan is an immune regulatory ligand for TLR2 and TLR4.

Particulate β-glucans enhanced NF-κB expression in cell-lines co-expressing Dectin-1A-TLR4 and Dectin-1B-TLR4, while soluble β-glucans only synergistically acted on Dectin-1A-TLR4. This was different with Dectin-1 co-expressing TLR2 and TLR5, which inhibited activation after particulate and soluble β-glucan stimulation. The co-acting effect of extracellular TLR2, TLR4 and TLR5 and Dectin-1 by particulate and soluble β-glucan on cytokine production was confirmed in THP-1 macrophages. Dectin-1 activation by particulate β-glucans during TLR2 and TLR4 but not TLR5 blocking was shown to enhance the pro-inflammatory cytokines IL-6, IL-8 and TNF-α in THP-1 macrophages. This effect was stronger with particulate than with soluble β-glucan. The data demonstrate that β-glucans is an immune regulatory ligand for TLR2 and TLR4.