Modulation of human dendritic cell activity by Giardia and helminth antigens

Parasite Immunol. 2018 May;40(5):e12525. doi: 10.1111/pim.12525. Epub 2018 Apr 14.

Abstract

Giardia duodenalis is a common intestinal protozoan parasite known to modulate host immune responses, including dendritic cell (DC) function. Coinfections 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 upregulated 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.

Keywords: Giardia duodenalis; apoptosis; dendritic Cells; helminths; intestinal diseases; parasites.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Helminth / immunology*
  • Apoptosis / immunology
  • Ascaris suum / immunology*
  • Cells, Cultured
  • Dendritic Cells / immunology*
  • Giardia lamblia / immunology*
  • Giardiasis / immunology*
  • Giardiasis / parasitology
  • Giardiasis / pathology
  • Humans
  • Interleukin-12 Subunit p35 / metabolism
  • Interleukin-6 / metabolism
  • Lipopolysaccharides / immunology
  • Trichuris / immunology*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Antigens, Helminth
  • IL12A protein, human
  • IL6 protein, human
  • Interleukin-12 Subunit p35
  • Interleukin-6
  • Lipopolysaccharides
  • Tumor Necrosis Factor-alpha