重组日本血吸虫钙网蛋白（SjCRT）诱导小鼠树突状细胞成熟和 Th1 型免疫应答。
SjCRT, a recombinant Schistosoma japonicum calreticulin, induces maturation of dendritic cells and a Th1-polarized immune response in mice.
机构信息
Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Key Laboratory of Animal Parasitology, Ministry of Agriculture of China, Shanghai, 200241, China.
College of Life and Environmental Sciences, Shanghai Normal University, Shanghai, 250014, China.
出版信息
Parasit Vectors. 2017 Nov 13;10(1):570. doi: 10.1186/s13071-017-2516-7.
BACKGROUND
It is well known that immunization of radiation-attenuated (RA) schistosoma cercariae or schistosomula can induce high levels of protective immunity against schistosoma cercariae reinfection in many animals. Many studies have shown that the Th1 cellular immune response is crucial for the protective effect elicited by RA schistosomula. However, the molecular mechanism of this strong protective immunity remains unclear.
METHODS
The expression profiles of Schistosoma japonicum calreticulin (SjCRT) in RA and normal schistosoma-derived cells were investigated by flow cytometry. The effect of recombinant SjCRT (rSjCRT) on mouse dendritic cells (DCs) was determined by FACS, ELISA and RT-PCR analysis. We also analyzed the effects of SjCRT on the activation of spleen cells from mice immunized with rSjCRT by detecting lymphocyte proliferation and the cytokine profiles of splenocytes.
RESULTS
We found that the expression level of SjCRT in the cells from RA larvae was significantly higher than that in cells from normal schistosomula at early stages of development (day 4). The results of effect of rSjCRT on mouse DCs showed that rSjCRT could induce phenotypic and functional maturation of DCs, and SjCRT bound to the surface of DCs through the CD91 receptor and could be engulfed by DCs. The results of activation of splenocytes from mice immunized with rSjCRT also demonstrate that rSjCRT can effectively stimulate the proliferative response of splenic lymphocytes, elicit splenocytes from immunized mice to secrete high levels of IFN-γ, TNF-α and IL-4, and activate CD4+ T cells to produce high levels of IFN-γ.
CONCLUSION
SjCRT is one of the immunostimulatory molecules released from RA schistosomula cells, might play a crucial role in conferring a Th1-polarized immune response induced by RA cercariae/schistosomula in mice, and is a candidate molecule responsible for the high levels of protective immunity induced by RA schistosomula.
背景
众所周知，免疫减毒（RA）尾蚴或童虫可诱导许多动物对尾蚴再感染产生高水平的保护性免疫。许多研究表明，Th1 细胞免疫应答对于 RA 童虫诱导的保护性效应至关重要。然而，这种强烈的保护性免疫的分子机制尚不清楚。
方法
通过流式细胞术研究了 RA 和正常血吸虫来源细胞中日本血吸虫钙网蛋白（SjCRT）的表达谱。通过 FACS、ELISA 和 RT-PCR 分析确定重组 SjCRT（rSjCRT）对小鼠树突状细胞（DC）的影响。我们还通过检测淋巴细胞增殖和脾细胞细胞因子谱分析 SjCRT 对 rSjCRT 免疫小鼠脾细胞激活的影响。
结果
我们发现 RA 幼虫细胞中 SjCRT 的表达水平在早期发育（第 4 天）时明显高于正常童虫细胞。rSjCRT 对小鼠 DC 影响的结果表明，rSjCRT 可诱导 DC 的表型和功能成熟，SjCRT 通过 CD91 受体与 DC 结合，并可被 DC 吞噬。rSjCRT 免疫小鼠脾细胞激活的结果也表明，rSjCRT 能有效刺激脾淋巴细胞的增殖反应，引发免疫小鼠脾细胞分泌高水平的 IFN-γ、TNF-α和 IL-4，并激活 CD4+T 细胞产生高水平的 IFN-γ。
结论
SjCRT 是 RA 尾蚴细胞释放的免疫刺激分子之一，可能在 RA 尾蚴/童虫诱导的 Th1 极化免疫反应中发挥关键作用，是 RA 童虫诱导高水平保护性免疫的候选分子。
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