Distinct vitellogenin domains differentially regulate immunological outcomes in invertebrates.
Distinct vitellogenin domains differentially regulate immunological outcomes in invertebrates.
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不同的卵黄原蛋白结构域差异调节无脊椎动物的免疫结果
DOI：
10.1074/jbc.ra120.015686
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发表时间：
2021-01
期刊：
影响因子：
--
通讯作者：
Li W
中科院分区：
文献类型：
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作者：
Sun W;Li H;Zhao Y;Bai L;Qin Y;Wang Q;Li W
卵黄蛋白原(VG)的经典作用是为胚胎发育提供能量储备，但它的作用似乎超出了这一营养功能，它在宿主免疫防御中的重要性正受到越来越多的研究关注。然而，VG调节的免疫功能依赖于不同物种中的三个不同结构域，并且仍然知之甚少。在本研究中，我们确定了中华绒螯蟹中三个保守的VG结构域-LPD_N、DUF1943和VWD，突出了VG在脊椎动物和无脊椎动物中的功能相似性。在这三个结构域中，DUF1943和VWD通过与微生物表面的特征成分相互作用而显示出明确的细菌结合活性，但LPD_N结构域没有显示出这种活性。抗菌实验表明，只有VWD结构域能够抑制细菌的增殖，并且由于保守的氨基酸残基，这一功能在不同物种之间可能是保守的。为了进一步探讨VG与多聚体免疫球蛋白受体(PIgR)的关系，我们在HEK293T细胞中表达了EspIgR和三个中华艾美耳球虫VG(EsVg)结构域，免疫共沉淀实验表明只有DUF1943结构域与EspIgR相互作用。随后的实验证明，EsVg通过DUF1943结构域与EspIgR结合来调节血细胞吞噬功能，从而促进细菌清除，保护宿主免受细菌感染。据我们所知，我们的工作首次报道了VG中不同的结构域在无脊椎动物中诱导不同的免疫结果，为pIgR作为VG的吞噬受体提供了新的证据。
The classical role of Vitellogenin (Vg) is providing energy reserves for developing embryos, but its roles appear to extend beyond this nutritional function, and its importance in host immune defense is garnering increasing research attention. However, Vg-regulated immunological functions are dependent on three different domains within different species and remain poorly understood. In the present study, we confirmed three conserved VG domains—LPD_N, DUF1943, and VWD—in the Chinese mitten crab (Eriocheir sinensis), highlighting functional similarities of Vg in vertebrates and invertebrates. Of these three domains, DUF1943 and VWD showed definitive bacterial binding activity via interaction with the signature components on microbial surfaces, but this activity was not exhibited by the LPD_N domain. Antibacterial assays indicated that only the VWD domain inhibits bacterial proliferation, and this function may be conserved between different species due to the conserved amino acid residues. To further explore the relationship between Vg and polymeric immunoglobulin receptor (pIgR), we expressed EspIgR and the three E. sinensis Vg (EsVg) domains in HEK293T cells, and coimmunoprecipitation assay demonstrated that only the DUF1943 domain interacts with EspIgR. Subsequent experiments demonstrated that EsVg regulates hemocyte phagocytosis by binding with EspIgR through the DUF1943 domain, thus promoting bacterial clearance and protecting the host from bacterial infection. To the best of our knowledge, our work is the first to report distinct domains in Vg inducing different immunological outcomes in invertebrates, providing new evidence that pIgR acts as a phagocytic receptor for Vg.