MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.
State Key Laboratory of Veterinary Etiological Biology, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China.
Front Immunol. 2020 Jun 30;11:1388. doi: 10.3389/fimmu.2020.01388. eCollection 2020.
The α/β-hydrolase domain (ABHD) proteins belonging to α/β-hydrolase (ABH) superfamily are ubiquitously distributed throughout all the organisms, and their functional roles have been implicated in energy metabolism, cell signaling, growth and development. In our preliminary work, we identified a novel ABHD protein derived from excretory-secretory (ES) proteins (HcESPs) that interacted with host T cells. Here, we demonstrated that ABHD (HcABHD) protein, expressed in all life-cycle stages of , is a mammalian ABHD17 homolog with immunodiagnostic utility and lipase activity. Given its catalytic activities and immunomodulatory potentials, we further investigated the functional diversity of HcABHD as an individual ES protein in parasite-host interactions. HcABHD protein may serve as depalmitoylase or thioesterase to suppress cell viability, inhibit cell proliferation, induce intrinsic and extrinsic T cell apoptosis, and cause cell cycle arrested at G1 phase. Moreover, recombinant HcABHD stimuli exerted critical controls on T cell cytokine production profiles, predominantly by inhibiting the secretions of interleukin (IL)-4, interferon-gamma (IFN-γ) and transforming growth factor-beta (TGF-β) 1, and promoting IL-10 production. As the immunomodulator acting at the parasite-host interface, HcABHD protein may have potential applications for the vaccine development of therapeutic intervention. Together, these findings may help illuminate the molecular and particularly immunomodulatory aspects of ES proteins and contribute to an enhanced understanding of parasite immune evasion in -host biology.
α/β-水解酶结构域（ABHD）蛋白属于 α/β-水解酶（ABH）超家族，广泛分布于所有生物体中，其功能作用涉及能量代谢、细胞信号转导、生长和发育。在我们的初步研究中，我们鉴定了一种来自 排泄分泌（ES）蛋白（HcESPs）的新型 ABHD 蛋白，它与宿主 T 细胞相互作用。在这里，我们证明了 ABHD（HcABHD）蛋白在 的所有生命周期阶段都有表达，是一种具有免疫诊断效用和脂肪酶活性的哺乳动物 ABHD17 同源物。鉴于其催化活性和免疫调节潜力，我们进一步研究了 HcABHD 作为个体 ES 蛋白在寄生虫-宿主相互作用中的功能多样性。HcABHD 蛋白可能作为去棕榈酰酶或硫酯酶来抑制细胞活力、抑制细胞增殖、诱导内在和外在 T 细胞凋亡，并导致细胞周期停滞在 G1 期。此外，重组 HcABHD 刺激物对 T 细胞细胞因子产生谱发挥了关键的控制作用，主要通过抑制白细胞介素（IL）-4、干扰素-γ（IFN-γ）和转化生长因子-β（TGF-β）1 的分泌，并促进 IL-10 的产生。作为在寄生虫-宿主界面起作用的免疫调节剂，HcABHD 蛋白可能在治疗性疫苗开发方面具有应用潜力。总之，这些发现可能有助于阐明 ES 蛋白的分子特别是免疫调节方面，并有助于更好地理解寄生虫在宿主生物学中的免疫逃避。
