Trypanosomiasis is a devastating neglected tropical disease affecting livestock and humans. Humans are susceptible to two Trypanosoma brucei subspecies 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.

锥虫病是一种严重的被忽视的热带病，影响牲畜和人类。人类容易感染两种布鲁氏锥虫亚种，但通过循环称为锥虫溶解因子（TLFs）1和2的高密度脂蛋白（HDL）复合物而免受其他锥虫侵害。TLF包含有助于裂解的载脂蛋白L-1和触珠蛋白相关蛋白（HPR），它们可作为寄生虫受体的配体。TLF2还独特地包含非共价结合的免疫球蛋白M（IgM）抗体，其作用和来源尚不清楚。在这里，我们显示这些与TLF2相关的IgM与HPR和其他锥虫体表面蛋白（包括变异体表面糖蛋白）相互作用，可能促进复杂的生物发生和TLF对寄生虫的吸收。TLF2-IgM是种系抗体，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都是由锥虫感染引起的。