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

Background: Cystic 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). Results: Compared 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-β secretion and reduced of IL-4 levels in co-cultured T cells, ES-treated BMDCs did not modify their capacity to stimulate IFN-β or IL-4 production by T cells. Conclusions: We 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.