Schramm Gabriele, Mohrs Katja, Wodrich Maren, Doenhoff Michael J, Pearce Edward J, Haas Helmut, Mohrs Markus
Research Center Borstel, Borstel, Germany.
J Immunol. 2007 May 15;178(10):6023-7. doi: 10.4049/jimmunol.178.10.6023.
During infection with the helminth parasite Schistosoma mansoni, the deposition of eggs coincides with the onset of IL-4 production and Th2 development. Although IL-4 is known as a potent inducer of Th2 differentiation, the mechanism by which schistosome eggs induce IL-4 production is not clear. In this study, we demonstrate that the S. mansoni egg Ag (SmEA) induces IgE-dependent IL-4 production by basophils derived from Heligmosomoides polygyrus-infected or OVA/alum-immunized mice in the absence of pathogen-specific IgE. The effect is mediated by the secretory glycoprotein IPSE/alpha-1, because IPSE/alpha-1-depleted SmEA no longer induces cytokine production. Conversely, recombinant IPSE/alpha-1 is sufficient to induce IL-4 production. Importantly, the injection of SmEA or recombinant IPSE/alpha-1 into H. polygyrus-infected 4get/KN2 IL-4 reporter mice rapidly induces the dose-dependent IL-4 production by basophils in the liver, a major site of egg deposition. Thus, IPSE/alpha-1 induces basophils to produce IL-4 even in the absence of Ag-specific IgE.
在感染曼氏血吸虫这种蠕虫寄生虫期间，虫卵的沉积与白细胞介素-4（IL-4）产生及辅助性T细胞2（Th2）发育的起始同时发生。尽管IL-4是已知的Th2分化的强效诱导剂，但血吸虫卵诱导IL-4产生的机制尚不清楚。在本研究中，我们证明曼氏血吸虫卵抗原（SmEA）在没有病原体特异性IgE的情况下，可诱导来自多形螺旋线虫感染或卵清蛋白/明矾免疫小鼠的嗜碱性粒细胞产生依赖IgE的IL-4。该效应由分泌性糖蛋白IPSE/α-1介导，因为去除IPSE/α-1的SmEA不再诱导细胞因子产生。相反，重组IPSE/α-1足以诱导IL-4产生。重要的是，将SmEA或重组IPSE/α-1注射到多形螺旋线虫感染的4get/KN2 IL-4报告基因小鼠体内，可迅速诱导肝脏（虫卵沉积的主要部位）中的嗜碱性粒细胞产生剂量依赖性的IL-4。因此，即使在没有抗原特异性IgE的情况下，IPSE/α-1也能诱导嗜碱性粒细胞产生IL-4。
