Schistosoma mansoni soluble egg antigens are internalized by human dendritic cells through multiple C-type lectins and suppress TLR-induced dendritic cell activation

Ellis van Liempt, Sandra J van Vliet, Anneke Engering, Juan Jesus García Vallejo, Christine M C Bank, Marta Sanchez-Hernandez, Yvette van Kooyk, Irma van Die

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214 Citations (Scopus)

Abstract

In schistosomiasis, a parasitic disease caused by helminths, the parasite eggs induce a T helper 2 cell (T(H)2) response in the host. Here, the specific role of human monocyte-derived dendritic cells (DCs) in initiation and polarization of the egg-specific T cell responses was examined. We demonstrate that immature DCs (iDCs) pulsed with schistosome soluble egg antigens (SEA) do not show an increase in expression of co-stimulatory molecules or cytokines, indicating that no conventional maturation was induced. The ability of SEA to affect the Toll-like receptor (TLR) induced maturation of iDCs was examined by copulsing the DCs with SEA and TLR-ligands. SEA suppressed both the maturation of iDCs induced by poly-I:C and LPS, as indicated by a decrease in co-stimulatory molecule expression and production of IL-12, IL-6 and TNF-alpha. In addition, SEA suppressed T(H)1 responses induced by the poly-I:C-pulsed DCs, and skewed the LPS-induced mixed response towards a T(H)2 response. Immature DCs rapidly internalized SEA through the C-type lectins DC-SIGN, MGL and the mannose receptor and the antigens were targeted to MHC class II-positive lysosomal compartments. The internalization of SEA by multiple C-type lectins may be important to regulate the response of the iDCs to TLR-induced signals.

Original languageEnglish
Pages (from-to)2605-15
Number of pages11
JournalMolecular immunology
Volume44
Issue number10
DOIs
Publication statusPublished - Apr 2007

Keywords

  • Animals
  • Antigen Presentation
  • Antigens, Helminth/immunology
  • Cytokines/metabolism
  • Dendritic Cells/drug effects
  • Histocompatibility Antigens Class II/immunology
  • Humans
  • Lectins, C-Type/immunology
  • Ligands
  • Lipopolysaccharides/pharmacology
  • Lysosomal-Associated Membrane Protein 1/metabolism
  • Ovum/immunology
  • Poly I-C/pharmacology
  • Schistosoma mansoni/immunology
  • T-Lymphocytes/immunology
  • Toll-Like Receptors/immunology

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