TY - JOUR

T1 - Modulation of human dendritic cell activity by Giardia and helminth antigens

AU - Summan, Anneka

AU - Nejsum, Peter

AU - Williams, Andrew R

N1 - This article is protected by copyright. All rights reserved.

PY - 2018

Y1 - 2018

N2 - Giardia duodenalis is a common intestinal protozoan parasite known to modulate host immune responses, including dendritic cell (DC) function. Co-infections of intestinal pathogens are common, and thus DCs may be concurrently exposed to antigens from multiple parasites. Here, we investigated the effects of G. duodenalis products on human monocyte-derived DC function independently and in combination with helminth antigens (Ascaris suum and Trichuris suis). All antigens individually induced an anti-inflammatory phenotype in DCs, reducing lipopolysaccharide (LPS)-induced interleukin (IL)-6, IL-12p70 and tumour necrosis factor (TNF)-α secretion. G. duodenalis and T. suis products also consistently up-regulated IL-10 production. Despite a similar modulation of cytokine secretion, additive effects between Giardia and helminth products were not observed, indicating a dominant effect of a single parasite stimulus and limited interactive effects on DC function. G. duodenalis trophozoites induced rapid apoptosis in DCs, which was not observed with the helminth antigens suggesting that the modulatory effects of G. duodenalis may override that of A. suum and T. suis. Thus, G. duodenalis modulates DC activity by modulating cytokine secretion and/or inducing apoptosis, which may be a parasite driven mechanism to dampen host immunity and establish chronic infections. The differential mechanisms of DC modulation by intestinal parasites warrant further attention. This article is protected by copyright. All rights reserved.

AB - Giardia duodenalis is a common intestinal protozoan parasite known to modulate host immune responses, including dendritic cell (DC) function. Co-infections of intestinal pathogens are common, and thus DCs may be concurrently exposed to antigens from multiple parasites. Here, we investigated the effects of G. duodenalis products on human monocyte-derived DC function independently and in combination with helminth antigens (Ascaris suum and Trichuris suis). All antigens individually induced an anti-inflammatory phenotype in DCs, reducing lipopolysaccharide (LPS)-induced interleukin (IL)-6, IL-12p70 and tumour necrosis factor (TNF)-α secretion. G. duodenalis and T. suis products also consistently up-regulated IL-10 production. Despite a similar modulation of cytokine secretion, additive effects between Giardia and helminth products were not observed, indicating a dominant effect of a single parasite stimulus and limited interactive effects on DC function. G. duodenalis trophozoites induced rapid apoptosis in DCs, which was not observed with the helminth antigens suggesting that the modulatory effects of G. duodenalis may override that of A. suum and T. suis. Thus, G. duodenalis modulates DC activity by modulating cytokine secretion and/or inducing apoptosis, which may be a parasite driven mechanism to dampen host immunity and establish chronic infections. The differential mechanisms of DC modulation by intestinal parasites warrant further attention. This article is protected by copyright. All rights reserved.

U2 - 10.1111/pim.12525

DO - 10.1111/pim.12525

M3 - Journal article

C2 - 29574798

VL - 40

JO - Parasite Immunology

JF - Parasite Immunology

SN - 0141-9838

IS - 5

M1 - e12525

ER -