Variant surface glycoprotein density defines an immune evasion threshold for African trypanosomes undergoing antigenic variation.
Variant surface glycoprotein density defines an immune evasion threshold for African trypanosomes undergoing antigenic variation.
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DOI：
10.1038/s41467-017-00959-w
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发表时间：
2017-10-10
影响因子：
16.6
通讯作者：
Papavasiliou FN
中科院分区：
文献类型：
--
作者：
Pinger J;Chowdhury S;Papavasiliou FN
布氏锥虫是一种原生动物寄生虫，通过重复替换其大基因组VSG库中的致密变体表面糖蛋白（VSG）外壳来逃避其宿主的适应性免疫应答。虽然调节VSG基因表达和多样化的机制已被广泛研究，但在蛋白质水平上VSG外壳置换的动态以及该过程对成功免疫逃避的影响仍不清楚。在这里，我们评估的速度VSG更换锥虫表面的遗传VSG开关后，并表明，完全更换外套需要几天才能完成。使用体内感染试验，我们证明，寄生虫进行外套更换是唯一容易清除通过早期IgM抗体在有限的时间。最后，我们表明，IgM失去了它的能力，介导锥虫清除在出乎意料的早期阶段的外套更换的基础上的一个临界密度阈值，其同源VSGs的寄生虫表面。 布氏锥虫通过替换变异表面糖蛋白（VSG）外壳逃避宿主免疫系统。在这里，作者表明VSG替换需要几天才能完成，并且寄生虫在此过程中很短一段时间内容易受到宿主免疫系统的影响。
Trypanosoma brucei is a protozoan parasite that evades its host’s adaptive immune response by repeatedly replacing its dense variant surface glycoprotein (VSG) coat from its large genomic VSG repertoire. While the mechanisms regulating VSG gene expression and diversification have been examined extensively, the dynamics of VSG coat replacement at the protein level, and the impact of this process on successful immune evasion, remain unclear. Here we evaluate the rate of VSG replacement at the trypanosome surface following a genetic VSG switch, and show that full coat replacement requires several days to complete. Using in vivo infection assays, we demonstrate that parasites undergoing coat replacement are only vulnerable to clearance via early IgM antibodies for a limited time. Finally, we show that IgM loses its ability to mediate trypanosome clearance at unexpectedly early stages of coat replacement based on a critical density threshold of its cognate VSGs on the parasite surface. Trypanosoma brucei evades the host immune system through replacement of a variant surface glycoprotein (VSG) coat. Here, the authors show that VSG replacement takes several days to complete, and the parasite is vulnerable to the host immune system for a short period of time during the process.
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