Inducible Germline IgMs Bridge Trypanosome Lytic Factor Assembly and Parasite Recognition.
Inducible Germline IgMs Bridge Trypanosome Lytic Factor Assembly and Parasite Recognition.
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诱导种系 IgM 桥接锥虫裂解因子组装和寄生虫识别。
DOI：
10.1016/j.chom.2020.04.012
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发表时间：
2020
影响因子：
30.3
通讯作者：
Raper,Jayne
中科院分区：
文献类型：
--
作者：
Verdi,Joseph;Zipkin,Ronnie;Hillman,Elani;Gertsch,RahelA;Pangburn,SarahJ;Thomson,Russell;Papavasiliou,Nina;Sternberg,Jeremy;Raper,Jayne
锥虫病是一种被忽视的破坏性热带疾病，影响牲畜和人类。人类对两种布氏锥虫亚种易感，但通过循环高密度脂蛋白（HDL）复合物（称为锥虫溶解因子（TLF）1和2）保护免受其他锥虫感染。TLF含有有助于溶解的载脂蛋白L-1和触珠蛋白相关蛋白（HPR），其可作为寄生虫受体的配体发挥作用。TLF 2还独特地含有非共价结合的免疫球蛋白M（IgM）抗体，其作用和起源仍不清楚。在这里，我们表明，这些TLF 2相关的IgM相互作用与HPR和替代锥虫表面蛋白，包括变异的表面糖蛋白，可能促进复杂的生物合成和TLF吸收到寄生虫。TLF 2-IgM是生殖系抗体，虽然在健康个体中以基础浓度存在，但在鼠模型和人类昏睡病患者中由锥虫感染引起。这些数据表明，多反应性和自身反应性生殖系抗体，如TLF 2相关的IgM在抗微生物免疫中发挥作用。
Trypanosomiasis is a devastating neglected tropical disease affecting livestock and humans. Humans are susceptible to twoTrypanosoma bruceisubspecies but protected from other trypanosomes by circulating high-density lipoprotein (HDL) complexes called trypanosome lytic factors (TLFs) 1 and 2. TLFs contain apolipoprotein L-1 contributing to lysis and haptoglobin-related protein (HPR), which can function as a ligand for a parasite receptor. TLF2 also uniquely contains non-covalently associated immunoglobin M (IgM) antibodies, the role and origin of which remain unclear. Here, we show that these TLF2-associated IgMs interact with both HPR and alternate trypanosome surface proteins, including variant surface glycoprotein, likely facilitating complex biogenesis and TLF uptake into parasites. TLF2-IgMs are germline antibodies that, while present at basal concentrations in healthy individuals, are elicited by trypanosome infection in both murine models and human sleeping sickness patients. These data suggest that poly- and self-reactive germline antibodies such as TLF2-associated IgMs play a role in antimicrobial immunity.