A haptoglobin-hemoglobin receptor conveys innate immunity to Trypanosoma brucei in humans
A haptoglobin-hemoglobin receptor conveys innate immunity to Trypanosoma brucei in humans
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DOI：
10.1126/science.1156296
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发表时间：
2008-05-02
期刊：
影响因子：
56.9
通讯作者：
Pays, Etienne
中科院分区：
文献类型：
--
作者：
Vanhollebeke, Benoit;De Muylder, Geraldine;Pays, Etienne
原生动物寄生虫布氏锥虫被载脂蛋白L-I溶解，载脂蛋白L-I是人高密度脂蛋白（HDL）颗粒的一种成分，其特征还在于存在触珠蛋白相关蛋白。我们报告说，这一过程是由寄生虫糖蛋白受体介导的，该受体结合珠蛋白-血红蛋白复合物，具有高亲和力，用于血红素的摄取和掺入细胞内血红素蛋白。在小鼠中，这种受体是最佳寄生虫生长和寄生虫对宿主巨噬细胞氧化爆发的抵抗所必需的。在人类中，锥虫受体也识别血红蛋白和触珠蛋白相关蛋白之间的复合物，这解释了其捕获锥虫降解HDL的能力。因此，在人类中，触珠蛋白相关蛋白的存在转移了锥虫触珠蛋白-血红蛋白受体的功能，以引发针对寄生虫的先天宿主免疫。
The protozoan parasite Trypanosoma brucei is lysed by apolipoprotein L-I, a component of human high- density lipoprotein ( HDL) particles that are also characterized by the presence of haptoglobin- related protein. We report that this process is mediated by a parasite glycoprotein receptor, which binds the haptoglobin- hemoglobin complex with high affinity for the uptake and incorporation of heme into intracellular hemoproteins. In mice, this receptor was required for optimal parasite growth and the resistance of parasites to the oxidative burst by host macrophages. In humans, the trypanosome receptor also recognized the complex between hemoglobin and haptoglobin- related protein, which explains its ability to capture trypanolytic HDLs. Thus, in humans the presence of haptoglobin- related protein has diverted the function of the trypanosome haptoglobin- hemoglobin receptor to elicit innate host immunity against the parasite.