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Co‐operative suppression of inflammatory responses in human dendritic cells by plant proanthocyanidins and products from the parasitic nematode Trichuris suis
Author(s) -
Williams Andrew R.,
Klaver Elsenoor J.,
Laan Lisa C.,
Ramsay Aina,
Fryganas Christos,
Difborg Rolf,
Kringel Helene,
Reed Jess D.,
MuellerHarvey Irene,
Skov Søren,
van Die Irma,
Thamsborg Stig M.
Publication year - 2017
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12687
Subject(s) - immune system , lipopolysaccharide , proinflammatory cytokine , inflammation , secretion , biology , immunology , tumor necrosis factor alpha , antigen , microbiology and biotechnology , endocrinology
Summary Interactions between dendritic cells ( DC s) 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 DC s and subsequent T helper type 1 (Th1) ‐type responses in naive T cells. Moreover, we proposed that, because DC s 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 (Ts SP ). We show that PAC are endocytosed by monocyte‐derived DC s and selectively induce CD 86 expression. Subsequently, PAC suppress the LPS ‐induced secretion of interleukin‐6 ( IL ‐6) and IL ‐12p70, while enhancing secretion of IL ‐10. Incubation of DC s 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 DC s with Ts SP and PAC synergistically reduced secretion of tumour necrosis factor‐ α , IL ‐6 and IL ‐12p70 while increasing IL ‐10 secretion. Moreover, both Ts SP and PAC alone induced Th2‐associated OX 40L expression in DC s, and together synergized to up‐regulate OX 40L. These data suggest that PAC induce an anti‐inflammatory phenotype in human DC s that selectively down‐regulates Th1 response in naive T cells, and that they also act cooperatively with Ts SP . Our results indicate a novel interaction between dietary compounds and parasite products to influence immune function, and may suggest that combinations of PAC and Ts SP can have therapeutic potential for inflammatory disorders.