SjTat-TPI facilitates adaptive T-cell responses and reduces hepatic pathology during Schistosoma japonicum infection in BALB/c mice.

SjTat-TPI facilitates adaptive T-cell responses and reduces hepatic pathology during Schistosoma japonicum infection in BALB/c mice.
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SjTat-TPI 在 BALB/c 小鼠日本血吸虫感染期间促进适应性 T 细胞反应并减少肝脏病理。

DOI:
10.1186/s13071-015-1275-6
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发表时间:
2015-12-30
影响因子:
3.2
通讯作者:
Ji M
Ji M
中科院分区:
医学2区
文献类型:
--
作者:
Zhang W;Luo X;Zhang F;Zhu Y;Yang B;Hou M;Xu Z;Yu C;Chen Y;Chen L;Ji M

文献摘要

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血吸虫病是一种严重危害公共卫生和社会发展的寄生虫病。中国是日本血吸虫疫情最严重的国家之一,目前仍需要有效的疫苗。本研究采用tat介导的蛋白转导技术,探讨不同抗原提呈途径对宿主免疫应答的影响及对日本血吸虫感染的潜在保护作用。我们成功构建了重组日本血吸虫三磷酸酯异构酶(Tat-TPI)作为候选疫苗。无论是足垫注射Tat-TPI还是背部皮下注射Tat-TPI三次,小鼠腘窝引流淋巴结和脾脏均出现较强的CD8+T反应(Tc1)。不仅如此,它还能帮助CD4+T细胞产生比TPI免疫更多的IFN-γ。此外,它可以促进IgG的产生,特别是IgG1亚类。最重要的是,与tpi疫苗接种组或对照组相比,Tat-TPI免疫导致肝脏中单个鸡蛋肉芽肿的面积显着减小。然而,Tat-TPI诱导的抗感染效果仍然有限。本研究表明,融合TPI免疫可增强日本血吸虫感染后的CD4+ t细胞应答,减少肝卵肉芽肿面积,但未达到我们预期的日本血吸虫感染保护作用。最佳疫苗策略值得进一步研究。
Schistosomiasis is a kind of parasitic zoonoses which causes serious damage to public health and social development. China is one of the countries most affected by Schistosoma japonicum and an effective vaccine is still needed. In this study, we adopted Tat-mediated protein transduction technology to investigate the impact of different antigen presented approaches on host’s immune response and the potential protection against Schistosoma japonicum infection. We successfully constructed the recombinant S. japonicum triosephosphate isomerase, Tat-TPI, as a vaccine candidate. Whether injected with Tat-TPI in foot pad or vaccinated with Tat-TPI in the back subcutaneously for three times, the draining popliteal lymph nodes and spleen both developed a stronger CD8+T response (Tc1) in mice. Not only that, but it also helped CD4+T cells to produce more IFN-γ than TPI immunisation. In addition, it could boost IgG production, especially IgG1 subclass. Most importantly, Tat-TPI immunisation led to the significant smaller area of a single egg granuloma in the livers as compared with TPI-vaccinated or control groups. However, the anti-infection efficiency induced by Tat-TPI was still restricted. This study indicated that immunisation with Tat-fused TPI could contribute to enhance CD4+T-cell response and decrease hepatic egg granulomatous area after S. japonicum infection though it did not achieve our expected protection against Schistosoma japonicum infection. The optimal vaccine strategy warrants further research.