Parasitologie Fonctionnelle et Evolutive, UMR 5244, CNRS Université de Perpignan, Perpignan, France.
PLoS Negl Trop Dis. 2010 Sep 7;4(9):e813. doi: 10.1371/journal.pntd.0000813.
For many decades, invertebrate immunity was believed to be non-adaptive, poorly specific, relying exclusively on sometimes multiple but germ-line encoded innate receptors and effectors. But recent studies performed in different invertebrate species have shaken this paradigm by providing evidence for various types of somatic adaptations at the level of putative immune receptors leading to an enlarged repertoire of recognition molecules. Fibrinogen Related Proteins (FREPs) from the mollusc Biomphalaria glabrata are an example of these putative immune receptors. They are known to be involved in reactions against trematode parasites. Following not yet well understood somatic mechanisms, the FREP repertoire varies considerably from one snail to another, showing a trend towards an individualization of the putative immune repertoire almost comparable to that described from vertebrate adaptive immune system. Nevertheless, their antigenic targets remain unknown. In this study, we show that a specific set of these highly variable FREPs from B. glabrata forms complexes with similarly highly polymorphic and individually variable mucin molecules from its specific trematode parasite S. mansoni (Schistosoma mansoni Polymorphic Mucins: SmPoMucs). This is the first evidence of the interaction between diversified immune receptors and antigenic variant in an invertebrate host/pathogen model. The same order of magnitude in the diversity of the parasite epitopes and the one of the FREP suggests co-evolutionary dynamics between host and parasite regarding this set of determinants that could explain population features like the compatibility polymorphism observed in B. glabrata/S. mansoni interaction. In addition, we identified a third partner associated with the FREPs/SmPoMucs in the immune complex: a Thioester containing Protein (TEP) belonging to a molecular category that plays a role in phagocytosis or encapsulation following recognition. The presence of this last partner in this immune complex argues in favor of the involvement of the formed complex in parasite recognition and elimination from the host.
几十年来,人们一直认为无脊椎动物的免疫是非适应性的,特异性差,仅依赖于有时是多个但由种系编码的先天受体和效应物。但最近在不同无脊椎动物物种中进行的研究动摇了这一范式,为潜在免疫受体水平的各种类型的体节适应性提供了证据,从而导致识别分子的 repertoire 扩大。来自软体动物 B. glabrata 的纤维蛋白原相关蛋白 (FREP) 就是这些潜在免疫受体的一个例子。已知它们参与了针对吸虫寄生虫的反应。在尚未完全了解的体节机制作用下,FREP 的 repertoire 在不同的蜗牛之间差异很大,表现出一种几乎与脊椎动物适应性免疫系统所描述的个体化趋势相当的潜在免疫 repertoire 个体差异。然而,它们的抗原靶标仍然未知。在这项研究中,我们表明,来自 B. glabrata 的一组特定的高度可变的 FREP 与来自其特定吸虫寄生虫 S. mansoni 的高度多态和个体可变粘蛋白分子形成复合物(Schistosoma mansoni 多态粘蛋白:SmPoMucs)。这是首次在无脊椎动物宿主/病原体模型中观察到多样化的免疫受体与抗原变体相互作用的证据。寄生虫表位的多样性与 FREP 的多样性相同,表明宿主和寄生虫之间存在共同进化动态,这组决定因素可以解释群体特征,如在 B. glabrata/S. mansoni 相互作用中观察到的相容性多态性。此外,我们在免疫复合物中鉴定出与 FREP/SmPoMuc 相关的第三个伙伴:一种含有硫酯的蛋白 (TEP),属于在识别后参与吞噬作用或包裹作用的分子类别。该免疫复合物中最后一个伙伴的存在表明,形成的复合物参与了寄生虫的识别和从宿主中消除。