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.

Modulation of human dendritic cell activity by Giardia and helminth antigens

“…We used predetermined, moderate concentrations of each parasite antigen to ensure that we did not saturate the DC response; indeed preliminary experiments showed that higher concentrations of G. duodenalis and A. suum induced substantially more inhibition (close to 100%) of inflammatory cytokine production (our unpublished data). Moreover, we have previously demonstrated synergistic suppression of LPS‐induced IL‐6 and IL‐12p70 production by TsSP and plant polyphenols, confirming that DC activity can be simultaneously modulated by multiple external stimuli under these conditions . If the different parasite products interacted independently with DCs, by definition an additive reduction in cytokine secretion would have observed.…”

“…Moreover, we have previously demonstrated synergistic suppression of LPS-induced IL-6 and IL-12p70 production by TsSP and plant polyphenols, confirming that DC activity can be simultaneously modulated by multiple external stimuli under these conditions. 13 If the different parasite products interacted independently with DCs, by definition an additive reduction in cytokine secretion would have observed. Our results therefore suggest a degree of antagonism between the different parasite products, the reasons for which are not yet clear.…”

“…Monocyte‐derived DCs were produced as described previously . Briefly, PBMCs were isolated from buffy coats obtained from healthy, anonymous blood donors (Rigshospitalet, Copenhagen, Denmark), following written informed consent.…”

“…Monocyte-derived DCs were produced as described previously. 13 Briefly, PBMCs were isolated from buffy coats obtained from healthy, anonymous blood donors (Rigshospitalet, Copenhagen, Denmark), following written informed consent. Monocytes were purified using anti-CD14 microbeads (Miltenyi biotech), and immature DCs were differentiated by 4-5 days of culture with IL-4 and GM-CSF (R and D Systems, UK; both 12.5 ng/mL), which consistently resulted in pure DC cultures containing between 90%-99% CD11c + and MHC-II + cells ( Figure S1).…”

Benefits of Condensed Tannins in Forage Legumes Fed to Ruminants: Importance of Structure, Concentration, and Diet Composition

“…Niezen et al (2002) measured higher antibody titers against antigens to adult T. circumcincta and adult and larval T. colubriformis when lambs were fed with sulla compared with alfalfa. Moreover, recent in vitro studies have also indicated that CTs can directly modulate the activity of immune cells such as gd T cells and dendritic cells, potentially enhancing the host's innate immune response (Tibe et al, 2012;Williams et al, 2016Williams et al, , 2017. Moreover, recent in vitro studies have also indicated that CTs can directly modulate the activity of immune cells such as gd T cells and dendritic cells, potentially enhancing the host's innate immune response (Tibe et al, 2012;Williams et al, 2016Williams et al, , 2017.…”