Sialylated ligands on pathogenic Trypanosoma cruzi interact with Siglec-E (sialic acid-binding Ig-like lectin-E)
Sialylated ligands on pathogenic Trypanosoma cruzi interact with Siglec-E (sialic acid-binding Ig-like lectin-E)
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DOI：
10.1111/j.1462-5822.2009.01350.x
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发表时间：
2009-11-01
影响因子：
3.4
通讯作者：
Jacobs, Thomas
中科院分区：
文献类型：
--
作者：
Erdmann, Hanna;Steeg, Christiane;Jacobs, Thomas
克氏锥虫会抑制免疫系统，导致其在宿主细胞中的持续存在。T. Cruzi是一种主要的毒力因子，并将唾液酸从宿主糖缀合物转移到寄生虫上的粘蛋白样分子。在这里，我们证明了这些唾液酸化结构在免疫抑制中发挥作用。我们用了两个T。cruzi菌株的TS活性与其致病性相关。Tulahuen菌株，其特征在于高TS活性有效感染小鼠，而Tehuantepec菌株显示TS活性降低不能建立专利寄生虫血症。体外分析表明，这两种菌株以相当的速率侵入吞噬和非吞噬宿主细胞，但它们表现出不同的潜力，以调节树突状细胞的功能。与Tehuantepec相反，Tulahuen菌株抑制了促炎细胞因子IL-12的产生和随后的T细胞活化。这种抑制作用是不存在的寄生虫后去唾液酸化。因此，我们分析了T. cruzi与DC上的抑制性唾液酸结合蛋白Siglec-E相互作用。事实上，Siglec-E与致病性Tulahuen菌株相互作用，但显示与Tehuantepec菌株的结合减弱。使用抗体在DC上连接Siglec-E证实了这种对DC功能的抑制作用。
P>Trypanosoma cruzi causes a suppression of the immune system leading to persistence in host cells. The trans-sialidase expressed by T. cruzi is a major virulence factor and transfers sialic acid from host glycoconjugates to mucin-like molecules on the parasite. Here we demonstrate that these sialylated structures play a role in the immunosuppression. We used two T. cruzi strains, whose TS activity correlated with their pathogenicity. The Tulahuen strain, characterized by a high TS activity efficiently infected mice, whereas the Tehuantepec strain showing a reduced TS activity could not establish a patent parasitemia. In vitro analysis revealed that these two strains invaded phagocytic and non-phagocytic host cells at a comparable rate, but they exhibited different potentials to modulate dendritic cell function. In contrast to Tehuantepec, the Tulahuen strain suppressed the production of the proinflammatory cytokine IL-12 and subsequent T-cell activation. This inhibitory effect was absent upon desialylation of the parasite. Therefore, we analysed whether sialylated structures of T. cruzi interact with the inhibitory sialic acid-binding protein Siglec-E on DC. Indeed, Siglec-E interacted with the pathogenic Tulahuen strain, but showed a diminished binding to the Tehuantepec strain. Ligation of Siglec-E on DC using antibodies confirmed this inhibitory effect on DC function.