PDF(Pubmed)
Abstract：
African Trypanosomes have developed elaborate mechanisms to escape the adaptive immune response, but little is known about complement evasion particularly at the early stage of infection. Here we show that ISG65 of the human-infective parasite Trypanosoma brucei gambiense is a receptor for human complement factor C3 and its activation fragments and that it takes over a role in selective inhibition of the alternative pathway C5 convertase and thus abrogation of the terminal pathway. No deposition of C4b, as part of the classical and lectin pathway convertases, was detected on trypanosomes. We present the cryo-electron microscopy (EM) structures of native C3 and C3b in complex with ISG65 which reveal a set of modes of complement interaction. Based on these findings, we propose a model for receptor-ligand interactions as they occur at the plasma membrane of blood-stage trypanosomes and may facilitate innate immune escape of the parasite.
摘要：
非洲锥虫已经开发了复杂的机制来逃避适应性免疫反应，但是对补体逃避的了解很少，尤其是在感染的早期。在这里，我们表明，人类感染的寄生虫布氏冈比亚锥虫的ISG65是人类补体因子C3及其激活片段的受体，并且它在选择性抑制替代途径C5转化酶并因此废除终末途径中起作用。没有沉积C4b,作为经典和凝集素途径转化酶的一部分，在锥虫上检测到。我们介绍了天然C3和C3b与ISG65复合的低温电子显微镜（EM）结构，揭示了补体相互作用的一组模式。基于这些发现,我们提出了受体-配体相互作用的模型，因为它们发生在血液阶段锥虫的质膜上，并且可能促进寄生虫的先天免疫逃逸。
