Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QW, UK.
Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK.
Nat Commun. 2022 Aug 29;13(1):5085. doi: 10.1038/s41467-022-32728-9.
African trypanosomes are extracellular pathogens of mammals and are exposed to the adaptive and innate immune systems. Trypanosomes evade the adaptive immune response through antigenic variation, but little is known about how they interact with components of the innate immune response, including complement. Here we demonstrate that an invariant surface glycoprotein, ISG65, is a receptor for complement component 3 (C3). We show how ISG65 binds to the thioester domain of C3b. We also show that C3 contributes to control of trypanosomes during early infection in a mouse model and provide evidence that ISG65 is involved in reducing trypanosome susceptibility to C3-mediated clearance. Deposition of C3b on pathogen surfaces, such as trypanosomes, is a central point in activation of the complement system. In ISG65, trypanosomes have evolved a C3 receptor which diminishes the downstream effects of C3 deposition on the control of infection.
非洲锥虫是哺乳动物的细胞外病原体，会暴露于适应性免疫系统和固有免疫系统中。锥虫通过抗原变异来逃避适应性免疫反应，但对于它们如何与固有免疫反应的成分（包括补体）相互作用，人们知之甚少。在这里，我们证明了一种不变表面糖蛋白 ISG65 是补体成分 3 (C3) 的受体。我们展示了 ISG65 如何与 C3b 的硫酯域结合。我们还表明，在小鼠模型中，C3 有助于控制感染早期的锥虫，并提供证据表明 ISG65 参与降低锥虫对 C3 介导的清除的敏感性。C3b 在病原体表面（如锥虫）上的沉积是补体系统激活的关键点。在 ISG65 中，锥虫已经进化出一种 C3 受体，它降低了 C3 沉积对控制感染的下游影响。
