Pivotal roles of the parasite PGD2 synthase and of the host D prostanoid receptor 1 in schistosome immune evasion
Pivotal roles of the parasite PGD2 synthase and of the host D prostanoid receptor 1 in schistosome immune evasion
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DOI：
10.1002/eji.200324143
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发表时间：
2003-10-01
影响因子：
5.4
通讯作者：
Trottein, F
中科院分区：
文献类型：
--
作者：
Hervé, M;Angeli, V;Trottein, F
前列腺素（PG）是免疫和炎症反应的重要调节剂。我们最近证实，曼氏血吸虫（Schistosoma mansoni）产生的PGD（2）抑制表皮朗格汉斯细胞（LC）向引流淋巴结（DLN）的迁移。在这里，我们确定的负责寄生虫酶是一个28 kDa的谷胱甘肽-S-转移酶（称为Sm 28 GST）。皮内注射Sm 28 GST在野生型（WT），但不是在D前列腺素受体（DP）1-缺陷小鼠废除离开LC从表皮后TNF-α或FITC治疗。在感染期间，DP 1缺陷恢复LC迁移，但不提高皮肤DLN中T细胞增殖的速率。然而，相对于WT小鼠，来自DP 1缺陷型感染小鼠的DLN细胞产生显著更少的IFN-γ和IL-10，但产生等量的IL-4。有趣的是，感染的DP 1缺陷小鼠产生更多的Th 2偏向性体液免疫反应，寄生虫血症显著减少，肝脏和肠道中鸡蛋诱导的炎症反应减少。综上所述，我们认为Sm 28 GST衍生的PGD（2）激活DP 1可能代表了一种策略，使线粒体逃避宿主的免疫防御。我们还认为，DP 1是重要的Th 1/Th 2平衡的免疫反应和感染过程中的炎症反应。
Prostaglandins (PG) are important modulators of immune and inflammatory responses. We recently demonstrated that the production of PGD(2) by the helminthic parasite Schistosoma mansoni inhibits the migration of epidermal Langerhans cells (LC) to the draining lymph nodes (DLN). Here, we identify the responsible parasite enzyme as being a 28-kDa glutathione-S-transferase (termed Sm28GST). Intradermal injection of Sm28GST in wild-type (WT), but not in D prostanoid receptor (DP) 1-deficient mice abrogates the departure of LC from the epidermis after TNF-alpha or FITC treatment. During infection, DP1 deficiency restores LC migration, but does not enhance the rate of T cell proliferation in the skin DLN. However, relative to WT mice, DLN cells from DP1-deficient infected mice produce dramatically less IFN-gamma and IL-10, but equal amount of IL-4. Interestingly, infected DP1-deficient mice develop a more Th2-biased humoral immune response, a significantly reduced parasitemia and a decreased egg-induced inflammatory response in the liver and intestines. Taken together, we propose that DP1 activation by the Sm28GST-derived PGD(2) could represent a strategy for the schistosome to evade host immune defenses. We also suggest that DP1 is important in the Th1/Th2 balance of the immune response and in inflammatory reactions during infection.