Abstract/Summary

Interactions between dendritic cells (DCs) and environmental, dietary and pathogen antigens play a key role in immune homeostasis and regulation of inflammation. Dietary polyphenols such as proanthocyanidins (PAC) may reduce inflammation, and we therefore hypothesised that PAC may suppress lipopolysaccharide (LPS)-induced responses in human DCs and subsequent Th1-type responses in naïve T-cells. Moreover, we proposed that, since DCs are likely to be exposed to multiple stimuli, the activity of PAC may synergise with other bioactive molecules which have anti-inflammatory activity, e.g. soluble products from the helminth parasite Trichuris suis (TsSP). We show that PAC are endocytosed by monocyte-derived DCs and selectively induce CD86 expression. Subsequently, PAC suppress the LPS-induced secretion of IL-6 and IL-12p70, whilst enhancing secretion of IL-10. Incubation of DCs with PAC did not affect lymphocyte proliferation, however subsequent IFN-γ production was markedly suppressed, whilst IL-4 production was unaffected. The activity of PAC was confined to oligomers (degree of polymerization ≥ 4). Co-pulsing DCs with TsSP and PAC synergistically reduced secretion of TNF-α, IL-6 and IL-12p70 whilst increasing IL-10 secretion. Moreover, both TsSP and PAC alone induced Th2-associated OX40L expression in DCs, and together synergized to up-regulate OX40L. These data suggest that PAC induce an anti-inflammatory phenotype in human DCs that selectively down-regulates Th1 response in naïve T-cells, and that they also act cooperatively with TsSP. Our results indicate a novel interaction between dietary compounds and parasite products to influence immune function, and may suggest that combinations of PAC and TsSP can have therapeutic potential for inflammatory disorders.