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
Department of Molecular Cell Biology and Immunology, VU University Medical Center, van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands.
Mol Immunol. 2007 Apr;44(10):2605-15. doi: 10.1016/j.molimm.2006.12.012. Epub 2007 Jan 22.
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.
在由蠕虫引起的寄生虫病血吸虫病中，寄生虫卵会在宿主体内引发辅助性T2细胞（T(H)2）反应。在此，研究了人单核细胞衍生树突状细胞（DCs）在卵特异性T细胞反应的启动和极化中的具体作用。我们证明，用血吸虫可溶性卵抗原（SEA）脉冲处理的未成熟DCs（iDCs）未显示共刺激分子或细胞因子表达增加，这表明未诱导出传统的成熟。通过将DCs与SEA和Toll样受体（TLR）配体共同脉冲处理，研究了SEA影响TLR诱导的iDCs成熟的能力。SEA抑制了由多聚肌苷酸:胞苷酸（poly-I:C）和脂多糖（LPS）诱导的iDCs成熟，这表现为共刺激分子表达减少以及白细胞介素-12（IL-12）、白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）的产生减少。此外，SEA抑制了由poly-I:C脉冲处理的DCs诱导的T(H)1反应，并使LPS诱导的混合反应偏向T(H)2反应。未成熟DCs通过C型凝集素DC-SIGN、巨噬细胞半乳糖型C型凝集素（MGL）和甘露糖受体快速内化SEA，并且抗原被靶向到MHC II类阳性溶酶体区室。SEA被多种C型凝集素内化可能对调节iDCs对TLR诱导信号的反应很重要。
