关键词: Adherence Heparin-binding Invasion MIC3 ROP9 SAG2 Toxoplasma gondii Vaccine candidates

Mesh : Animals Antibodies, Protozoan Antigens, Protozoan / pharmacology Antimicrobial Cationic Peptides Blood Proteins Carrier Proteins Female Heparitin Sulfate / immunology Immunization / methods Membrane Glycoproteins / pharmacology Membrane Proteins / pharmacology Mice Mice, Inbred BALB C Protozoan Proteins / pharmacology Protozoan Vaccines / pharmacology Recombinant Proteins Toxoplasma / immunology Vaccines, DNA

来  源:   DOI:10.1016/j.actatropica.2019.01.001   PDF(Sci-hub)

Abstract:
Toxoplasma gondii (T. gondii) is an obligatory intracellular parasite that can infect varieties of warm-blooded animals, including humans and birds. Heparan sulfate (HS) is widely distributed on the eukaryotic cell surface of vertebrates and can inhibit T. gondii invasion. In this study, we investigated the transcription and expression of the level of TgROP9, TgMIC3, and TgSAG2 in T. gondii RH strain, and found that the expression levels of these three proteins in invading parasites were higher compared to those free ranging parasites. The recombinant proteins showed specific binding activity to both heparin and host cell surface. Incubation of these proteins with the host cells could block T. gondiiinvasion. Furthermore, protein-specific antibodies also blocked parasite invasion. Antibodies in the sera of T. gondii infected individuals recognized the recombinant TgROP9, TgMIC3, and TgSAG2, which suggested the exposure of these proteins to human immune system. Mice immunized with the three proteins exhibited protective immunity against lethal challenge. The data collectively suggested that these parasitic proteins may be used as candidate antigens for development of anti-toxoplasmosis vaccine.
摘要:
弓形虫(T.gondii)是一种强制性的细胞内寄生虫,可以感染各种温血动物,包括人类和鸟类。硫酸乙酰肝素(HS)广泛分布于脊椎动物真核细胞表面,具有抑制弓形虫入侵的作用。在这项研究中,我们研究了TgROP9,TgMIC3和TgSAG2在弓形虫RH菌株中的转录和表达,并发现这三种蛋白质在入侵寄生虫中的表达水平高于那些自由放养的寄生虫。重组蛋白对肝素和宿主细胞表面均显示出特异性结合活性。将这些蛋白质与宿主细胞一起孵育可以阻断弓形虫入侵。此外,蛋白质特异性抗体也阻断寄生虫的入侵。弓形虫感染个体血清中的抗体识别重组TgROP9,TgMIC3和TgSAG2,这表明这些蛋白质暴露于人类免疫系统。用这三种蛋白质免疫的小鼠表现出针对致死攻击的保护性免疫力。数据共同表明,这些寄生蛋白可用作开发抗弓形虫病疫苗的候选抗原。
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