Faveeuw Christelle, Mallevaey Thierry, Paschinger Katharina, Wilson Iain B H, Fontaine Josette, Mollicone Rosella, Oriol Rafael, Altmann Friedrich, Lerouge Patrice, Capron Monique, Trottein François
Inserm U547, IFR17, Institut Pasteur de Lille, Lille, France.
Eur J Immunol. 2003 May;33(5):1271-81. doi: 10.1002/eji.200323717.
During murine schistosomiasis, egg-derived glycoconjugates play a key role in skewing the immune response towards a Th2 phenotype. Among the candidates responsible for this effect, complex-type N-glycans containing the core alpha 3-fucose and core beta 2-xylose determinants, two glycan epitopes found in some invertebrate- and plant-derived allergens, may be important. Here, we show that core alpha 3-fucose and core beta 2-xylose determinants are expressed in the different developmental stages of Schistosoma mansoni, particularly in the excretory-secretory systems of schistosomula and adult worms and in eggs deposited in the liver. Glycosyltransferase assays confirmed the presence of core alpha 3-fucosyltransferase and core beta 2-xylosyltransferase activities in egg extracts. Using a model of immunization with pulsed dendritic cells, we show that egg-derived glycoproteins containing the core alpha 3-fucose and core beta 2-xylose determinants generate a strong Th2-biased cellular response in mice and that the glycan moieties of this extract are important in this effect. During murine infection, these complex-type N-glycans induce a glycan-specific Th2 cellular response and elicit T-dependent anti-core alpha 3-fucose and anti-core beta 2-xylose IgG1 (a Th2-associated isotype), but not IgG2b (a Th1-associated isotype) Ab. Taken together, our results point out the importance of core fucosylated/xylosylated N-glycans in the Th2 immune response during murine schistosomiasis.
在小鼠血吸虫病期间，卵源性糖缀合物在使免疫反应偏向Th2表型方面发挥关键作用。在造成这种效应的候选物质中，含有核心α3-岩藻糖和核心β2-木糖决定簇的复合型N-聚糖可能很重要，这两种聚糖表位存在于一些无脊椎动物和植物源性过敏原中。在此，我们表明核心α3-岩藻糖和核心β2-木糖决定簇在曼氏血吸虫的不同发育阶段均有表达，尤其在童虫和成虫的排泄分泌系统以及沉积在肝脏中的虫卵中。糖基转移酶测定证实了虫卵提取物中存在核心α3-岩藻糖基转移酶和核心β2-木糖基转移酶活性。使用脉冲树突状细胞免疫模型，我们发现含有核心α3-岩藻糖和核心β2-木糖决定簇的卵源性糖蛋白在小鼠中产生强烈的Th2偏向性细胞反应，且该提取物的聚糖部分在此效应中很重要。在小鼠感染期间，这些复合型N-聚糖诱导聚糖特异性Th2细胞反应，并引发T细胞依赖性抗核心α3-岩藻糖和抗核心β2-木糖IgG1（一种与Th2相关的同种型）抗体产生，但不产生IgG2b（一种与Th1相关的同种型）抗体。综上所述，我们的结果指出了核心岩藻糖基化/木糖基化N-聚糖在小鼠血吸虫病Th2免疫反应中的重要性。
