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日本血吸虫紫外线减毒尾蚴尽管上调了C57BL/6小鼠细胞毒性相关基因的表达,但仍无法有效诱导Th1反应。

Ultraviolet- attenuated cercariae of Schistosoma japonicum fail to effectively induce a Th1 response in spite of up-regulating expression of cytotoxicity-related genes in C57BL/6 mice.

作者信息

Zhang Meijuan, Tian Fang, Gao Yanan, Ji Minjun, Wu Guanling

机构信息

Department of Pathogen Biology and Immunology, Nanjing Medical University, Nanjing 210029, Jiangsu Province, China ; Department of Clinical Laboratory, the first Affliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China.

出版信息

J Biomed Res. 2010 Jul;24(4):277-84. doi: 10.1016/S1674-8301(10)60039-5.

Abstract

OBJECTIVE

To better understand the reason that Schistosoma japonicum (S. japonicum) ultraviolet (UV)-radiated cercariae could not induce high level of protection in C57BL/6 mice.

METHODS

Microarray technology was performed to investigate the gene transcription profile in skin draining lymph nodes (sdLNs) at 1 w after exposure to attenuated cercariae (AC) or normal cercariae (NC) of S. japonicum in C57BL/6 mice. The expressions of some representative genes were further confirmed by real-time PCR. Subsequently, the expressions of Th1/Th2 cytokine genes, cytotoxicity-related genes, as well as co-stimulator genes in spleens from AC-vaccinated and NC-infected mice were analyzed by real-time PCR at w 3 and 6 post-exposure.

RESULTS

The gene expressions of Th1 cytokines, including interferon-γ (IFN-γ), interleukin (IL)-12 and tumor necrosis factor-α (TNF-α) in the sdLNs were significantly lower in AC-vaccinated mice than in NC-infected mice. Furthermore, the gene expressions of Th1- and Th2- cytokines, including IFN-γ, IL-12, TNF-α, IL-4 and IL-10, in the spleens from AC-vaccinated mice showed little changes at w 3 and 6 post-vaccination. In addition, cytotoxicity-related molecules including granzyme A, granzyme B, granzyme K, perforin 1 and Fas L were up-regulated from the early stage of vaccination, and peaked at the 3(rd) w after vaccination with UV-AC.

CONCLUSION

UV-AC of S. japonicum could not effectively induce a Th1 response in C57BL/6 mice, which may be an explanation for the low protection against parasite challenge, and the role played by up-regulated expression of cytotoxicity-related genes in mice needs to be further investigated.

摘要

目的

为了更好地理解日本血吸虫紫外线(UV)照射尾蚴不能在C57BL/6小鼠中诱导高水平保护的原因。

方法

利用基因芯片技术研究C57BL/6小鼠在暴露于日本血吸虫减毒尾蚴(AC)或正常尾蚴(NC)后1周时皮肤引流淋巴结(sdLNs)中的基因转录谱。通过实时PCR进一步确认一些代表性基因的表达。随后,在暴露后第3周和第6周,通过实时PCR分析AC疫苗接种小鼠和NC感染小鼠脾脏中Th1/Th2细胞因子基因、细胞毒性相关基因以及共刺激基因的表达。

结果

AC疫苗接种小鼠sdLNs中Th1细胞因子的基因表达,包括干扰素-γ(IFN-γ)、白细胞介素(IL)-12和肿瘤坏死因子-α(TNF-α),显著低于NC感染小鼠。此外,AC疫苗接种小鼠脾脏中Th1和Th2细胞因子的基因表达,包括IFN-γ、IL-12、TNF-α、IL-4和IL-10,在接种后第3周和第6周变化不大。另外,包括颗粒酶A、颗粒酶B、颗粒酶K、穿孔素1和Fas L在内的细胞毒性相关分子从疫苗接种早期就上调,并在UV-AC疫苗接种后第3周达到峰值。

结论

日本血吸虫UV-AC不能在C57BL/6小鼠中有效诱导Th1反应,这可能是对寄生虫攻击保护作用低的一个解释,细胞毒性相关基因在小鼠中上调表达所起的作用需要进一步研究。

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