Impairment of dendritic cell function and induction of CD4+CD25+Foxp3+ T cells by excretory-secretory products: a potential mechanism of immune evasion adopted by Echinococcus granulosus

Abstract

BackgroundCystic echinococcosis, caused by infection with Echinococcus granulosus, is one of the most widespread zoonotic helminth diseases. Modulation of host responses is an important strategy used by helminth parasites to promote infection. To better understand the mechanisms adopted by E. granulosus to escape host immune responses, we investigated the effects of excretory–secretory products (ES) and adult worm antigen (AWA) derived from adult E. granulosus on murine bone marrow-derived dendritic cells (BMDC).ResultsCompared with lipopolysaccharide (LPS), AWA, but not ES, induced BMDC maturation or stimulated BMDC cytokine production and co-stimulatory molecule expression (CD40, CD80 and MHC class II). Furthermore, ES-treated BMDCs pulsed with ovalbumin exhibited reduced co-stimulatory molecule expression in comparison with untreated BMDC, even in the presence of the strong Th1 inducer, CpG. Moreover, we detected the effects of ES-treated DC on T cell activation by an in vitro T cell priming assay. We observed that ES-treated BMDC co-cultured with DO11.10 transgenic CD4+ T cells induced the generation of CD4+CD25+Foxp3+ T cells. In addition, in contrast to AWA-treated BMDCs, which had markedly induced IFN-γ secretion and reduced of IL-4 levels in co-cultured T cells, ES-treated BMDCs did not modify their capacity to stimulate IFN-γ or IL-4 production by T cells.ConclusionsWe conclude that ES of adult E. granulosus inhibited DC function, impaired the development of Th1 cells induced by CpG, and induced CD4+CD25+Foxp3+ regulatory T cells in an IL-10-independent manner.

Zoonotic intestinal helminths interact with the canine immune system by modulating T cell responses and preventing dendritic cell maturation

“…Moreover, parasites can support Treg generation by modulating DCs, for example by preventing their maturation, which may then guide naïve T cells to differentiate into a regulatory subset. This has been illustrated for H. polygyrus or Echinococcus granulosus in which treatment of DCs with respective ES antigens elevate their Treg-inducing capacities 57 , 58 . The results presented here show both AcES and TcES to impair upregulation of MHC-II and CD80 after TLR4 stimulation, thus implicating A. caninum and T. canis to be capable of reducing DC maturation in dogs.…”

Characterization of the inflammatory cell infiltrate and expression of costimulatory molecules in chronic echinococcus granulosus infection of the human liver

“…The involvement of DCs in immunopathology of chronic CE has not been thoroughly studied yet. The only available data show the ability of parasite antigens to induce alternative differentiation of murine and human DCs in vitro , which results in overproduction of CD86 and downregulation of CD1a and their enhanced ability to activate Th2 or T reg responses [ 23 , 55 – 57 ]. Altogether, results of the present study could also imply the crucial role of DCs in the tissue-specific immune response in human chronic CE of the liver.…”

In vitro culture of Mesocestoides corti metacestodes and isolation of immunomodulatory excretory–secretory products

“…The phenotype observed is consistent with that of DCs exposed to metacestodes of Echinococcus spp . and Taenia spp . , highlighting the relevance of our observation in the general understanding of the host immunosuppression by metacestodes.…”