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

Immunology. 2017 Mar;150(3):312-328. doi: 10.1111/imm.12687. Epub 2016 Nov 30.


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.

Keywords: Trichuris suis; dendritic cells; inflammation; parasite; proanthocyanidins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Antigens, Helminth / immunology
  • Cells, Cultured
  • Cytokines / metabolism
  • Dendritic Cells / drug effects*
  • Dendritic Cells / immunology
  • Dendritic Cells / parasitology
  • Drug Therapy, Combination
  • Humans
  • Inflammation / drug therapy*
  • Inflammation / immunology
  • Lymphocyte Activation
  • OX40 Ligand / genetics
  • OX40 Ligand / metabolism
  • Proanthocyanidins / pharmacology*
  • RNA Interference
  • Swine
  • Th1 Cells / immunology*
  • Th1-Th2 Balance / drug effects
  • Th2 Cells / immunology*
  • Trichuriasis / drug therapy*
  • Trichuriasis / immunology
  • Trichuris / immunology
  • Up-Regulation


  • Anti-Inflammatory Agents
  • Antigens, Helminth
  • Cytokines
  • OX40 Ligand
  • Proanthocyanidins
  • TNFSF4 protein, human