当前位置: X-MOL 学术Int. J. Med. Microbiol. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Immunostimulatory efficacy and protective potential of putative TgERK7 protein in mice experimentally infected by Toxoplasma gondii.
International Journal of Medical Microbiology ( IF 4.1 ) Pub Date : 2020-05-30 , DOI: 10.1016/j.ijmm.2020.151432
Zhong-Yuan Li 1 , Hai-Ting Guo 2 , Guillermo Calderón-Mantilla 3 , Jun-Jun He 4 , Jin-Lei Wang 4 , Boyan B Bonev 5 , Xing-Quan Zhu 4 , Hany M Elsheikha 6
Affiliation  

The extracellular signal-regulated kinases (ERKs) serve as important determinants of cellular signal transduction pathways, and hence may play important roles during infections. Previous work suggested that putative ERK7 of Toxoplasma gondii is required for efficient intracellular replication of the parasite. However, the antigenic and immunostimulatory properties of TgERK7 protein remain unknown. The objective of this study was to produce a recombinant TgERK7 protein in vitro and to evaluate its effect on the induction of humoral and T cell-mediated immune responses against T. gondii infection in BALB/c mice. Immunization using TgERK7 mixed with Freund's adjuvants significantly increased the ratio of CD3e+CD4+ T/CD3e+CD8a+ T lymphocytes in spleen and elevated serum cytokines (IFN-γ, IL-2, IL-4, IL-10, IL-12p70, IL-23, MCP-1, and TNF-α) in immunized mice compared to control mice. On the contrary, immunization did not induce high levels of serum IgG antibodies. Five predicted peptides of TgERK7 were synthesized and conjugated with KLH and used to analyze the antibody specificity in the sera of immunized mice. We detected a progressive increase in the antibody level only against TgERK7 peptide A (DEVDKHVLRKYD). Antibody raised against this peptide significantly decreased intracellular proliferation of T. gondii in vitro, suggesting that peptide A can potentially induce a protective antibody response. We also showed that immunization improved the survival rate of mice challenged with a virulent strain and significantly reduced the parasite cyst burden within the brains of chronically infected mice. Our data show that TgERK7-based immunization induced TgERK7 peptide A-specific immune responses that can impart protective immunity against T. gondii infection. The therapeutic potential of targeting ERK7 signaling pathway for future toxoplasmosis treatment is warranted.



中文翻译:

弓形虫实验感染的小鼠中推定的TgERK7蛋白的免疫刺激功效和保护潜力。

细胞外信号调节激酶(ERK)是细胞信号转导途径的重要决定因素,因此可能在感染过程中发挥重要作用。先前的工作表明,弓形虫的推定ERK7是寄生虫有效细胞内复制所必需的。但是,Tg ERK7蛋白的抗原和免疫刺激特性仍然未知。这项研究的目的是在体外生产重组Tg ERK7蛋白并评估其对BALB / c小鼠中针对弓形虫感染的体液和T细胞介导的免疫反应的诱导作用。使用Tg免疫ERK7与弗氏佐剂混合可显着增加脾脏中CD3e + CD4 + T / CD3e + CD8a + T淋巴细胞的比例,并升高血清细胞因子(IFN-γ,IL-2,IL-4,IL-10,IL-12p70,IL与对照小鼠相比,免疫小鼠中的-23,MCP-1和TNF-α)。相反,免疫没有诱导高水平的血清IgG抗体。合成了五个预测的Tg ERK7肽,并与KLH偶联,用于分析免疫小鼠血清中的抗体特异性。我们检测到仅针对Tg ERK7肽A(DEVDKHVLRKYD)的抗体水平逐渐升高。针对这种肽的抗体显着降低了其细胞内增殖刚地弓形虫体外,表明肽A可以潜在地诱导保护性抗体应答。我们还表明,免疫接种提高了用强毒株攻击的小鼠的存活率,并显着降低了慢性感染小鼠脑内的寄生虫囊肿负担。我们的数据表明,基于Tg ERK7的免疫诱导了Tg ERK7肽A特异性免疫应答,该应答可赋予针对弓形虫感染的保护性免疫。靶向ERK7信号通路的未来弓形虫病的治疗潜力是有保证的。

更新日期:2020-05-30
down
wechat
bug