title: Co-operative suppression of inflammatory responses in human dendritic cells by plant proanthocyanidins and products from the parasitic nematode Trichuris suis.
abstract: 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 hypothesized that PAC may suppress lipopolysaccharide (LPS) -induced responses in human DCs and subsequent T helper type 1 (Th1) -type responses in naive T cells. Moreover, we proposed that, because DCs are likely to be exposed to multiple stimuli, the activity of PAC may synergise with other bioactive molecules that 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 interleukin-6 (IL-6) and IL-12p70, while enhancing secretion of IL-10. Incubation of DCs with PAC did not affect lymphocyte proliferation; however, subsequent interferon-γ production was markedly suppressed, while 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 tumour necrosis factor-α, IL-6 and IL-12p70 while 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 naive 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.
authors.affiliation: Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg C, Denmark.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Williams
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Centre, Amsterdam, the Netherlands.
authors.forename: Elsenoor J
authors.initials: EJ
authors.lastname: Klaver
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Centre, Amsterdam, the Netherlands.
authors.forename: Lisa C
authors.initials: LC
authors.lastname: Laan
authors.affiliation: Chemistry and Biochemistry Laboratory, University of Reading, Reading, UK.
authors.forename: Aina
authors.initials: A
authors.lastname: Ramsay
authors.affiliation: Chemistry and Biochemistry Laboratory, University of Reading, Reading, UK.
authors.forename: Christos
authors.initials: C
authors.lastname: Fryganas
authors.affiliation: Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg C, Denmark.
authors.forename: Rolf
authors.initials: R
authors.lastname: Difborg
authors.affiliation: Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg C, Denmark.
authors.forename: Helene
authors.initials: H
authors.lastname: Kringel
authors.affiliation: Department of Animal Science, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: Jess D
authors.initials: JD
authors.lastname: Reed
authors.affiliation: Chemistry and Biochemistry Laboratory, University of Reading, Reading, UK.
authors.forename: Irene
authors.initials: I
authors.lastname: Mueller-Harvey
authors.affiliation: Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg C, Denmark.
authors.forename: Søren
authors.initials: S
authors.lastname: Skov
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Centre, Amsterdam, the Netherlands.
authors.forename: Irma
authors.initials: I
authors.lastname: van Die
authors.affiliation: Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg C, Denmark.
authors.forename: Stig M
authors.initials: SM
authors.lastname: Thamsborg
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000947:Antigens, Helminth / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000469:parasitology; D004359:Drug Therapy, Combination; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000276:immunology; D008213:Lymphocyte Activation; D053278:OX40 Ligand / Q000235:genetics / Q000378:metabolism; D044945:Proanthocyanidins / Q000494:pharmacology*; D034622:RNA Interference; D013552:Swine; D018417:Th1 Cells / Q000276:immunology*; D058408:Th1-Th2 Balance / Q000187:drug effects; D018418:Th2 Cells / Q000276:immunology*; D014257:Trichuriasis / Q000188:drug therapy* / Q000276:immunology; D014258:Trichuris / Q000276:immunology; D015854:Up-Regulation
chemical_list: D000893:Anti-Inflammatory Agents; D000947:Antigens, Helminth; D016207:Cytokines; D053278:OX40 Ligand; D044945:Proanthocyanidins; C089251:TNFSF4 protein, human
keywords: 
  Trichuris suis
  ; dendritic cells; inflammation; parasite; proanthocyanidins