...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Malaria hemozoin is immunologically inert but radically enhances innate responses by presenting malaria DNA to Toll-like receptor 9
【24h】

Malaria hemozoin is immunologically inert but radically enhances innate responses by presenting malaria DNA to Toll-like receptor 9

机译：疟原虫具有免疫惰性，但通过向Toll样受体9呈递疟疾DNA可以从根本上增强先天应答。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Hemozoin (HZ) is an insoluble crystal formed in the food vacuole of malaria parasites. HZ has been reported to induce inflammation by directly engaging Toll-like receptor (TLR) 9, an endosomal receptor. "Synthetic" HZ (β-hematin), typically generated from partially purified extracts of bovine hemin, is structurally identical to natural HZ. When HPLC-purified hemin was used to synthesize the crystal, β-hematin had no inflammatory activity. In contrast, natural HZ from Plasmodium faldparum cultures was a potent TLR9 inducer. Natural HZ bound recombinant TLR9 ectodomain, but not TLR2. Both TLR9 stimulation and TLR9 binding of HZ were abolished by nuclease treatment. PCR analysis demonstrated that natural HZ is coated with malarial but not human DNA. Purified malarial DNA activated TLR9 but only when DNA was targeted directly to the endosome with a transfection reagent. Stimulatory quantities of natural HZ contain < 1 μg of malarial DNA; its potency in activating immune responses was even greater than transfecting malarial DNA. Thus, although the malarial genome is extremely AT-rich, its DNA is highly proinflammatory, with the potential to induce cytokinemia and fever during disease. However, its activity depends on being bound to HZ, which we propose amplifies the biological responses to malaria DNA by targeting it to a TLR9~+ intracellular compartment.
机译：血红蛋白（HZ）是在疟原虫的食物液泡中形成的不溶晶体。据报道，HZ通过直接与内体受体Toll样受体（TLR）9结合来诱导炎症。通常由部分纯化的牛血红素提取物产生的“合成” HZ（β-hematin）在结构上与天然HZ相同。当使用HPLC纯化的血红素合成晶体时，β-血红素没有发炎活性。相反，来自恶性疟原虫培养物的天然HZ是有效的TLR9诱导剂。天然HZ结合重组TLR9胞外域，但不结合TLR2。通过核酸酶处理消除了TLR9刺激和HZ的TLR9结合。 PCR分析表明，天然HZ带有疟疾而不是人类DNA。纯化的疟疾DNA会激活TLR9，但仅当DNA用转染试剂直接靶向内体时才如此。刺激量的天然HZ含有<1μg的疟疾DNA；其激活免疫应答的能力甚至比转染疟疾DNA更大。因此，尽管疟疾基因组非常富含AT，但其DNA具有高度促炎性，并有可能在疾病期间诱发细胞分裂症和发烧。然而，其活性取决于与HZ的结合，我们建议通过将其靶向TLR9 +细胞内区室来扩大对疟疾DNA的生物学反应。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号