Schistosoma mansoni soluble egg antigens are internalized by human dendritic cells through multiple C-type lectins and suppress TLR-induced dendritic cell activation.
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.
van Liempt
Ellis
E
Department of Molecular Cell Biology and Immunology, VU University Medical Center, van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands.
van Vliet
Sandra J
SJ
Engering
Anneke
A
García Vallejo
Juan Jesus
JJ
Bank
Christine M C
CM
Sanchez-Hernandez
Marta
M
van Kooyk
Yvette
Y
van Die
Irma
I
D000818:Animals; D017951:Antigen Presentation; D000947:Antigens, Helminth / Q000276:immunology* / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D037181:Lectins, C-Type / Q000276:immunology*; D008024:Ligands; D008070:Lipopolysaccharides / Q000494:pharmacology; D052118:Lysosomal-Associated Membrane Protein 1 / Q000378:metabolism; D010063:Ovum / Q000276:immunology; D011070:Poly I-C / Q000494:pharmacology; D012550:Schistosoma mansoni / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D051193:Toll-Like Receptors / Q000276:immunology*
D000947:Antigens, Helminth; D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D037181:Lectins, C-Type; D008024:Ligands; D008070:Lipopolysaccharides; D052118:Lysosomal-Associated Membrane Protein 1; D051193:Toll-Like Receptors; D011070:Poly I-C