Intraperitoneal murine Echinococcus multilocularis infection induces differentiation of TGF-β-expressing DCs that...

Intraperitoneal larval infection (alveolar echinococcosis, AE) with Echinococcus multilocularis in mice impairs host immunity. Metacestode metabolites may modulate immunity putatively via dendritic cells. During murine AE, a relative increase of peritoneal DCs (pe-DCs) in infected mice (AE-pe-DCs; 4% of total peritoneal cells) as compared to control mice (naïve pe-DCs; 2%) became apparent in our study. The differentiation of AE-pe-DCs into TGF-β-expressing cells and the higher level of IL-4 than IFN-γ/IL-2 mRNA expression in AE-CD4+pe-T cells indicated a Th2 orientation. Analysis of major accessory molecule expression on pe-DCs from AE-infected mice revealed that CD80 and CD86 were down-regulated on AE-pe-DCs, while ICAM-1(CD54) remained practically unchanged. Moreover, AE-pe-DCs had a weaker surface expression of MHC class II (Ia) molecules as compared to naïve pe-DCs. The gene expression level of molecules involved in MHC class II (Ia) synthesis and formation of MHC class II (Ia)-peptide complexes were down-regulated. In addition, metacestodes excreted/secreted (E/S) or vesicle-fluid (V/F) antigens were found to alter MHC class II molecule expression on the surface of BMDCs. Finally, conversely to naïve pe-DCs, an increasing number of AE-pe-DCs down-regulated Con A-induced proliferation of naïve CD4+pe-T cells. These findings altogether suggested that TGF-β-expressing immature AE-pe-DCs might play a significant role in the generation of a regulatory immune response within the peritoneal cavity of AE-infected mice.