Distinct patterns of dendritic cell cytokine release stimulated by beta-glucans and Toll-Like receptor agonists (98.33)

Abstract

Abstract β-glucans (βGs) derived from fungal cell walls have potential uses as immunomodulating agents and vaccine adjuvants. Yeast glucan particles (YGPs) are purified Saccharomyces cerevisiae cell walls treated so they are >80% β1,3-D-glucan and free of mannan and proteins. YGPs stimulated secretion of the proinflammatory cytokine TNF-α in wild type murine bone marrow-derived myeloid DCs (BMDCs), but did not stimulate IL-12p70 production. A purified soluble βG, scleroglucan, also stimulated TNF-α in BMDCs. These two βGs failed to stimulate TNF-α in dectin-1 (βG-receptor) knockout BMDCs. Co-stimulation of wild-type BMDCs with βGs and specific TLR ligands resulted in greatly enhanced TNF-α production but decreased IL-12p70 production compared with TLR ligands alone. The up-regulation of TNF-α and down-regulation IL-12p70 required dectin-1, but not IL-10. Similar patterns of cytokine regulation were observed in human monocyte-derived DCs (hDCs) co-stimulated with YGPs and, the TLR4 ligand, LPS. Finally, co-stimulation of BMDCs with the TLR9 ligand, CpG, and YGPs resulted in upregulated secretion of IL-1α and IL-10, downregulated IL-1β, IL-6 and IP-10, and had no significant effects on IL-12p40, KC, MCP-1 or MIP-α, compared with CpG alone. Thus, βGs have disparate effects on cytokine responses following DC stimulation with TLR ligands.