Hu Shaomin, Yang Linlin, Wu Zhongdao, Wong Chung Sing, Fung Ming Chiu
Department of Biology, the Chinese University of Hong Kong, Hong Kong, China.
J Parasitol. 2012 Apr;98(2):274-83. doi: 10.1645/GE-2692.1. Epub 2011 Oct 21.
Despite the great effort that has been given to control the disease, schistosomiasis remains the most important human helminth infection in terms of morbidity and mortality. Natural infection of schistosomes induces very little protective immunity against reinfection. Moreover, effective schistosome vaccines for practical use have not been developed. These parasites appear to have evolved highly effective modulatory mechanisms on their host's immune system that promote the parasites' survival and also hinder the development of effective strategies for treatment of the disease. Understanding of the mechanisms of schistosome-mediated immune modulation would be most helpful in schistosomiasis prevention and control. Previously, we have identified from Schistosoma japonicum an anti-inflammatory protein, Sj16, which suppresses thioglycollate-induced peritoneal inflammation in BALB/c mice, as well as thioglycollate-mediated peritoneal macrophage maturation, while modulating cytokine and chemokine production from peritoneal cells. In the present study, we have further investigated the modulatory effect of Sj16 on the host's adaptive immunity to heterologous antigens with the use of recombinant Sj16 (rSj16) expressed and purified from Escherichia coli . Results from this study indicate that rSj16 significantly suppresses antibody production, in addition to Th1 and Th2 responses to heterologous antigens in the BALB/c mouse model. Our study also reveals that rSj16 suppresses lipopolysaccharide-induced major histocompatibility complex II expression and IL-12 production, while increasing IL-10 production in resident peritoneal macrophages. These results may partially explain why parasite-related antigens cannot mount a protective immunity during early stages of schistosome infection.
尽管在控制该疾病方面付出了巨大努力，但就发病率和死亡率而言，血吸虫病仍然是最重要的人类蠕虫感染。血吸虫的自然感染诱导的针对再感染的保护性免疫非常少。此外，尚未开发出实际可用的有效血吸虫疫苗。这些寄生虫似乎已经在其宿主免疫系统上进化出了高效的调节机制，这些机制既促进了寄生虫的存活，也阻碍了该疾病有效治疗策略的发展。了解血吸虫介导的免疫调节机制对血吸虫病的预防和控制将非常有帮助。此前，我们从日本血吸虫中鉴定出一种抗炎蛋白Sj16，它可抑制BALB/c小鼠中巯基乙酸盐诱导的腹膜炎症以及巯基乙酸盐介导的腹膜巨噬细胞成熟，同时调节腹膜细胞中细胞因子和趋化因子的产生。在本研究中，我们使用从大肠杆菌中表达和纯化的重组Sj16（rSj16）进一步研究了Sj16对宿主针对异源抗原的适应性免疫的调节作用。这项研究的结果表明，除了在BALB/c小鼠模型中对异源抗原的Th1和Th2反应外，rSj16还能显著抑制抗体产生。我们的研究还表明，rSj16抑制脂多糖诱导的主要组织相容性复合体II表达和IL-12产生，同时增加驻留腹膜巨噬细胞中IL-10的产生。这些结果可能部分解释了为什么寄生虫相关抗原在血吸虫感染的早期阶段不能引发保护性免疫。
