Helminth antigens modulate TLR-initiated dendritic cell activation
Helminth antigens modulate TLR-initiated dendritic cell activation
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DOI：
10.4049/jimmunol.173.12.7454
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发表时间：
2004-12-15
影响因子：
4.4
通讯作者：
Pearce, EJ
中科院分区：
文献类型：
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作者：
Kane, CM;Cervi, L;Pearce, EJ
越来越多的人意识到蠕虫感染可以改善促炎性疾病。在某种程度上，这是由于它们固有的诱导Th 2和调节性T细胞应答的能力。然而，最近的证据表明，蠕虫对先天免疫反应也有直接的抗炎作用。在这项研究中，我们解决了这个问题，并表明，从蠕虫寄生虫曼氏血吸虫（SEA）的鸡蛋可溶性分子抑制LPS诱导的激活未成熟的小鼠树突状细胞，包括MHC II类，共刺激分子的表达，和IL-12的生产。SEA增强的LPS诱导的IL-10的产生部分地负责所观察到的LPS诱导的IL-12产生的减少。然而，IL-10（-/-）DC的分析揭示了SEA的独特的IL-10非依赖性抑制作用。IL-10非依赖性机制在TLR配体诱导的MAPK和NF-κ B信号通路的抑制中是明显的。微阵列分析表明，SEA单独独特地改变了一小部分基因的表达，这些基因在常规TLR诱导的DC成熟过程中不上调。相反，SEA对TLR配体诱导的DC活化的作用是显著的：当与LPS混合时，SEA显著影响>100个LPS调节的基因的表达。这些发现表明SEA通过直接调节DC响应TLR配体的能力而发挥有效的抗炎作用。
There is increasing awareness that helminth infections can ameliorate proinflammatory conditions. In part, this is due to their inherent ability to induce Th2 and, perhaps, regulatory T cell responses. However, recent evidence indicates that helminths also have direct anti-inflammatory effects on innate immune responses. In this study, we address this issue and show that soluble molecules from the eggs of the helminth parasite Schistosoma mansoni (SEA) suppress LPS-induced activation of immature murine dendritic cells, including MHC class II, costimulatory molecule expression, and IL-12 production. SEA-augmented LPS-induced production of IL-10 is in part responsible for the observed reduction in LPS-induced IL-12 production. However, analyses of IL-10(-/-) DC revealed distinct IL-10-independent suppressive effects of SEA. IL-10-independent mechanisms are evident in the suppression of TLR ligand-induced MAPK and NF-kappaB signaling pathways. Microarray analyses demonstrate that SEA alone uniquely alters the expression of a small subset of genes that are not up-regulated during conventional TLR-induced DC maturation. In contrast, the effects of SEA on TLR ligand-induced DC activation were striking: when mixed with LPS, SEA significantly affects the expression of >100 LPS-regulated genes. These findings indicate that SEA exerts potent anti-inflammatory effects by directly regulating the ability of DC to respond to TLR ligands.