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

Research output: Contribution to journalArticleAcademicpeer-review

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

Cite this

@article{9de4069166994655b0800b43e236605d,
title = "Schistosoma mansoni soluble egg antigens are internalized by human dendritic cells through multiple C-type lectins and suppress TLR-induced dendritic cell activation",
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.",
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",
author = "{van Liempt}, Ellis and {van Vliet}, {Sandra J} and Anneke Engering and {Garc{\'i}a Vallejo}, {Juan Jesus} and Bank, {Christine M C} and Marta Sanchez-Hernandez and {van Kooyk}, Yvette and {van Die}, Irma",
year = "2007",
month = "4",
doi = "10.1016/j.molimm.2006.12.012",
language = "English",
volume = "44",
pages = "2605--15",
journal = "Molecular Immunology",
issn = "0161-5890",
publisher = "Elsevier Limited",
number = "10",

}

Schistosoma mansoni soluble egg antigens are internalized by human dendritic cells through multiple C-type lectins and suppress TLR-induced dendritic cell activation. / van Liempt, Ellis; van Vliet, Sandra J; Engering, Anneke; García Vallejo, Juan Jesus; Bank, Christine M C; Sanchez-Hernandez, Marta; van Kooyk, Yvette; van Die, Irma.

In: Molecular Immunology, Vol. 44, No. 10, 04.2007, p. 2605-15.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Schistosoma mansoni soluble egg antigens are internalized by human dendritic cells through multiple C-type lectins and suppress TLR-induced dendritic cell activation

AU - van Liempt, Ellis

AU - van Vliet, Sandra J

AU - Engering, Anneke

AU - García Vallejo, Juan Jesus

AU - Bank, Christine M C

AU - Sanchez-Hernandez, Marta

AU - van Kooyk, Yvette

AU - van Die, Irma

PY - 2007/4

Y1 - 2007/4

N2 - 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.

AB - 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.

KW - Animals

KW - Antigen Presentation

KW - Antigens, Helminth/immunology

KW - Cytokines/metabolism

KW - Dendritic Cells/drug effects

KW - Histocompatibility Antigens Class II/immunology

KW - Humans

KW - Lectins, C-Type/immunology

KW - Ligands

KW - Lipopolysaccharides/pharmacology

KW - Lysosomal-Associated Membrane Protein 1/metabolism

KW - Ovum/immunology

KW - Poly I-C/pharmacology

KW - Schistosoma mansoni/immunology

KW - T-Lymphocytes/immunology

KW - Toll-Like Receptors/immunology

U2 - 10.1016/j.molimm.2006.12.012

DO - 10.1016/j.molimm.2006.12.012

M3 - Article

VL - 44

SP - 2605

EP - 2615

JO - Molecular Immunology

JF - Molecular Immunology

SN - 0161-5890

IS - 10

ER -