Co-operative suppression of inflammatory responses in human dendritic cells by proanthocyanidins and products from the parasitic nematode Trichuris suis

Williams , A. R., Klaver, E. J., Laan, L. C., Ramsay, A., Fryganas, C., Difborg , R., Kringel , H., Reed, J. D., Mueller-Harvey, I., Skov, S., van Die, I. and Thamsborg, S. M. (2017) Co-operative suppression of inflammatory responses in human dendritic cells by proanthocyanidins and products from the parasitic nematode Trichuris suis. Immunology, 150 (3). pp. 312-328. ISSN 1365-2567 doi: 10.1111/imm.12687

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.

Item Type	Article
URI	https://centaur.reading.ac.uk/id/eprint/67951
Identification Number/DOI	10.1111/imm.12687
Refereed	Yes
Divisions	Interdisciplinary Research Centres (IDRCs) > The Pearl Interdisciplinary centres and themes > Food Chain and Health Life Sciences > School of Agriculture, Policy and Development > Department of Animal Sciences > Animal, Dairy and Food Chain Sciences (ADFCS)- DO NOT USE
Publisher	Wiley
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