Institute of Infection and Immunology Research and Centre for Immunity, Infection and Evolution, School of Biological Sciences, University of Edinburgh, Edinburgh, EH9 3JT, UK.
Department of Clinical Surgery, University of Edinburgh, Edinburgh, EH16 4TJ, UK.
Nat Commun. 2017 Nov 23;8(1):1741. doi: 10.1038/s41467-017-01886-6.
Helminth parasites defy immune exclusion through sophisticated evasion mechanisms, including activation of host immunosuppressive regulatory T (Treg) cells. The mouse parasite Heligmosomoides polygyrus can expand the host Treg population by secreting products that activate TGF-β signalling, but the identity of the active molecule is unknown. Here we identify an H. polygyrus TGF-β mimic (Hp-TGM) that replicates the biological and functional properties of TGF-β, including binding to mammalian TGF-β receptors and inducing mouse and human Foxp3 Treg cells. Hp-TGM has no homology with mammalian TGF-β or other members of the TGF-β family, but is a member of the complement control protein superfamily. Thus, our data indicate that through convergent evolution, the parasite has acquired a protein with cytokine-like function that is able to exploit an endogenous pathway of immunoregulation in the host.
寄生虫通过复杂的逃避机制来对抗免疫排斥，包括激活宿主免疫抑制性调节性 T（Treg）细胞。鼠寄生虫旋毛虫可以通过分泌激活 TGF-β 信号的产物来扩大宿主 Treg 群体，但活性分子的身份尚不清楚。在这里，我们鉴定出一种旋毛虫 TGF-β 模拟物（Hp-TGM），它复制了 TGF-β 的生物学和功能特性，包括与哺乳动物 TGF-β 受体结合并诱导鼠和人 Foxp3 Treg 细胞。Hp-TGM 与哺乳动物 TGF-β 或 TGF-β 家族的其他成员没有同源性，但它是补体控制蛋白超家族的成员。因此，我们的数据表明，通过趋同进化，寄生虫获得了一种具有细胞因子样功能的蛋白质，能够利用宿主内的内源性免疫调节途径。
