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

Parasite Immunol. 2011 Sep;33(9):471-82. doi: 10.1111/j.1365-3024.2011.01303.x.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B7-1 Antigen / immunology
  • B7-2 Antigen / immunology
  • Blotting, Western
  • Bone Marrow Cells / immunology
  • CD4-Positive T-Lymphocytes / immunology
  • Cell Differentiation*
  • Cell Proliferation
  • Cytokines / metabolism
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology*
  • Disease Models, Animal
  • Down-Regulation
  • Echinococcosis
  • Echinococcosis, Hepatic / immunology
  • Echinococcosis, Hepatic / parasitology
  • Echinococcus multilocularis / immunology*
  • Echinococcus multilocularis / pathogenicity
  • Female
  • Flow Cytometry
  • Gene Expression Regulation
  • Histocompatibility Antigens Class II / immunology
  • Host-Parasite Interactions
  • Lymphocyte Activation
  • Membrane Proteins / isolation & purification
  • Mice
  • Mice, Inbred C57BL
  • Peritoneal Cavity / cytology
  • Peritoneal Cavity / parasitology*
  • RNA, Messenger / metabolism
  • Transforming Growth Factor beta / immunology*

Substances

  • B7-1 Antigen
  • B7-2 Antigen
  • Cytokines
  • Histocompatibility Antigens Class II
  • Membrane Proteins
  • RNA, Messenger
  • Transforming Growth Factor beta

Supplementary concepts

  • Alveolar echinococcosis