Layland Laura E, Wagner Hermann, da Costa Clarissa U Prazeres
Institute of Medical Microbiology, Immunology and Hygiene, Technical University of Munich, Munich, Germany.
Eur J Immunol. 2005 Nov;35(11):3248-57. doi: 10.1002/eji.200526273.
To evaluate the role of the innate immune system during schistosomiasis in vivo, we infected myeloid differentiation factor 88 (MyD88)-deficient mice with Schistosoma mansoni and analyzed their pathognomonic formation of hepatic granulomas and T cell responses. Even though the differences between knockout and wild-type mice in terms of mortality, liver damage, serum IgE and parasite burden were insignificant, the liver granulomas in the MyD88-deficient mice were significantly smaller, less cellular and contained a reduced percentage of eosinophils. Histologically, these granulomas revealed stronger fibrosis, confirmed also by increased levels of soluble collagen and IL-13, implying a Th2 bias. Spleen cells from infected MyD88-deficient mice also produced significantly less IFN-gamma than their wild-type controls upon restimulation with Schistosoma-egg-antigen (SEA). Furthermore, SEA-loaded APC from naive wild-type or MyD88-deficient mice induced equal amounts of proliferation and cytokine secretion by T cells from wild-type infected mice. In contrast, Ag-specific T cells from infected MyD88-deficient mice produced hardly any IFN-gamma but considerably more IL-10, again regardless of the APC type. These findings indicate that the loss of IFN-gamma production is not due to impaired antigen presentation but may perhaps is due to suppression by IL-10-producing T cells. Thus, MyD88 plays an important role in cellular infiltration, granuloma composition and T cell responses during schistosomiasis.
为了评估先天性免疫系统在血吸虫病体内过程中的作用，我们用曼氏血吸虫感染了髓样分化因子88（MyD88）缺陷小鼠，并分析了它们肝脏肉芽肿的病理形成和T细胞反应。尽管敲除小鼠和野生型小鼠在死亡率、肝损伤、血清IgE和寄生虫负荷方面的差异不显著，但MyD88缺陷小鼠的肝脏肉芽肿明显更小、细胞更少且嗜酸性粒细胞百分比降低。组织学上，这些肉芽肿显示出更强的纤维化，可溶性胶原蛋白和IL-13水平升高也证实了这一点，这意味着存在Th2偏向。在用血吸虫卵抗原（SEA）再次刺激后，感染MyD88缺陷小鼠的脾细胞产生的IFN-γ也明显少于野生型对照。此外，来自未感染的野生型或MyD88缺陷小鼠的负载SEA的抗原呈递细胞（APC）诱导来自感染野生型小鼠的T细胞产生等量的增殖和细胞因子分泌。相反，来自感染MyD88缺陷小鼠的抗原特异性T细胞几乎不产生任何IFN-γ，但产生的IL-10要多得多，同样与APC类型无关。这些发现表明，IFN-γ产生的丧失不是由于抗原呈递受损，而是可能由于产生IL-10的T细胞的抑制。因此，MyD88在血吸虫病期间的细胞浸润、肉芽肿组成和T细胞反应中起重要作用。
