The Immunomodulatory Effect of IrSPI, a Tick Salivary Gland Serine Protease Inhibitor Involved in Ixodes ricinus Tick Feeding
The Immunomodulatory Effect of IrSPI, a Tick Salivary Gland Serine Protease Inhibitor Involved in Ixodes ricinus Tick Feeding
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DOI：
10.3390/vaccines7040148
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发表时间：
2019-12-01
期刊：
影响因子：
7.8
通讯作者：
Bonnet, Sarah, I
中科院分区：
文献类型：
--
作者：
Blisnick, Adrien A.;Simo, Ladislav;Bonnet, Sarah, I
蜱是影响世界范围内家畜和野生动物的最重要的病原体载体。硬蜱喂养是一个缓慢的过程，需要几天时间，并需要对宿主反应进行扩展控制。喂食过程的成功取决于蜱唾液的注射，其不仅控制宿主止血和伤口愈合，而且还破坏宿主免疫反应以避免蜱排斥，从而为多种蜱传播病原体的生存和繁殖创造有利的生态位。在这里，我们报告的蓖麻硬蜱丝氨酸蛋白酶抑制剂（IrSPI）的分子和生化特性和功能。我们将IrSPI描述为一种Kunitz弹性蛋白酶抑制剂，在吸血过程中在几个蜱器官（特别是唾液腺）中过表达。我们还证明，当IrSPI通过唾液注射到宿主体内时，它对组织因子途径诱导的凝血、纤溶、内皮细胞血管生成或凋亡没有影响，但该蛋白具有免疫调节活性。特别是，IrSPI抑制CD 4（+）T淋巴细胞的增殖和脾细胞和巨噬细胞的促炎细胞因子分泌。我们的研究为蜱-宿主相互作用提供了有价值的知识，并提供了可以进一步利用的见解，以设计针对这种免疫调节剂的抗蜱疫苗。蓖麻取食
Ticks are the most important vectors of pathogens affecting both domestic and wild animals worldwide. Hard tick feeding is a slow process-taking up to several days-and necessitates extended control over the host response. The success of the feeding process depends upon injection of tick saliva, which not only controls host hemostasis and wound healing, but also subverts the host immune response to avoid tick rejection that creates a favorable niche for the survival and propagation of diverse tick-borne pathogens. Here, we report on the molecular and biochemical features and functions of an Ixodes ricinus serine protease inhibitor (IrSPI). We characterize IrSPI as a Kunitz elastase inhibitor that is overexpressed in several tick organs-especially salivary glands-during blood-feeding. We also demonstrated that when IrSPI is injected into the host through saliva, it had no impact on tissue factor pathway-induced coagulation, fibrinolysis, endothelial cell angiogenesis or apoptosis, but the protein exhibits immunomodulatory activity. In particular, IrSPI represses proliferation of CD4(+) T lymphocytes and proinflammatory cytokine secretion from both splenocytes and macrophages. Our study contributes valuable knowledge to tick-host interactions and provides insights that could be further exploited to design anti-tick vaccines targeting this immunomodulator implicated in I. ricinus feeding.