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Dietary polyphenols such as proanthocyanidins (PAC<\/jats:styled-content>) may reduce inflammation, and we therefore hypothesized that PAC<\/jats:styled-content> may suppress lipopolysaccharide (LPS<\/jats:styled-content>) \u2010induced responses in human DC<\/jats:styled-content>s and subsequent T helper type 1 (Th1) \u2010type responses in naive T cells. Moreover, we proposed that, because DC<\/jats:styled-content>s are likely to be exposed to multiple stimuli, the activity of PAC<\/jats:styled-content> may synergise with other bioactive molecules that have anti\u2010inflammatory activity, e.g. soluble products from the helminth parasite Trichuris suis<\/jats:italic> (TsSP<\/jats:styled-content>). We show that PAC<\/jats:styled-content> are endocytosed by monocyte\u2010derived DC<\/jats:styled-content>s and selectively induce CD<\/jats:styled-content>86 expression. Subsequently, PAC<\/jats:styled-content> suppress the LPS<\/jats:styled-content>\u2010induced secretion of interleukin\u20106 (IL<\/jats:styled-content>\u20106) and IL<\/jats:styled-content>\u201012p70, while enhancing secretion of IL<\/jats:styled-content>\u201010. Incubation of DC<\/jats:styled-content>s with PAC<\/jats:styled-content> did not affect lymphocyte proliferation; however, subsequent interferon\u2010\u03b3<\/jats:italic> production was markedly suppressed, while IL<\/jats:styled-content>\u20104 production was unaffected. The activity of PAC<\/jats:styled-content> was confined to oligomers (degree of polymerization \u2265 4). Co\u2010pulsing DC<\/jats:styled-content>s with TsSP<\/jats:styled-content> and PAC<\/jats:styled-content> synergistically reduced secretion of tumour necrosis factor\u2010\u03b1<\/jats:italic>, IL<\/jats:styled-content>\u20106 and IL<\/jats:styled-content>\u201012p70 while increasing IL<\/jats:styled-content>\u201010 secretion. Moreover, both TsSP<\/jats:styled-content> and PAC<\/jats:styled-content> alone induced Th2\u2010associated OX<\/jats:styled-content>40L expression in DC<\/jats:styled-content>s, and together synergized to up\u2010regulate OX<\/jats:styled-content>40L. These data suggest that PAC<\/jats:styled-content> induce an anti\u2010inflammatory phenotype in human DC<\/jats:styled-content>s that selectively down\u2010regulates Th1 response in naive T cells, and that they also act cooperatively with TsSP<\/jats:styled-content>. Our results indicate a novel interaction between dietary compounds and parasite products to influence immune function, and may suggest that combinations of PAC<\/jats:styled-content> and TsSP<\/jats:styled-content> can have therapeutic potential for inflammatory disorders.<\/jats:p>","DOI":"10.1111\/imm.12687","type":"journal-article","created":{"date-parts":[[2016,11,7]],"date-time":"2016-11-07T16:06:44Z","timestamp":1478534804000},"page":"312-328","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Co\u2010operative suppression of inflammatory responses in human dendritic cells by plant proanthocyanidins and products from the parasitic nematode Trichuris suis<\/i>"],"prefix":"10.1111","volume":"150","author":[{"given":"Andrew R.","family":"Williams","sequence":"first","affiliation":[{"name":"Department of Veterinary Disease Biology Faculty of Health and Medical Sciences University of Copenhagen Frederiksberg C 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