香菇多糖抗小鼠急性弓形虫感染免疫机制的初步探讨

A preliminary look at the immune mechanism by which lentinan inhibits acute infection with Toxoplasma gondii in mice

目的从香菇多糖对弓形虫感染小鼠Th1/Th2免疫应答建立的影响及二者平衡维持的角度探讨香菇多糖抗小鼠急性弓形虫感染的免疫机制。方法 RH株弓形虫速殖子腹腔感染小鼠前及感染后进行香菇多糖处理,观察各组小鼠的存活率,同时用ELISA法动态检测小鼠脾细胞培养液中Th1/Th2免疫反应关键细胞因子IFN-γ/IL-4水平及血清中IgG2a/IgG1抗体的含量。结果与对照组相比香菇多糖可以明显提高两处理组小鼠的存活率,香菇多糖处理组(LTN组)第10d全部死亡,而香菇多糖预处理组(pre-6dLTN组)第13d存活率仍达18.4%;pre-6dLTN组及LTN组在感染后第3d建立Th1型免疫应答,IFN-γ含量分别为186.28pg/ml及117.07pg/ml,与对照组相比差异有统计学意义(P<0.01);IgG2a含量为0.332(A490)及0.320(A490),与对照组相比差异有统计学意义(P<0.01),且于第7d达峰值。同时Th2型免疫应答开始建立,IL-4含量分别为121.28pg/ml及94.47pg/ml,与对照组相比差异有统计学意义(P<0.01);IgG1含量分别为0.382(A490)及0.354(A490),与对照组相比差异有统计学意义(P<0.05),随后维持较高水平。结论香菇多糖能辅助小鼠建立Th1/Th2免疫应答,且能适时转化并维持二者平衡,避免因任何一种免疫反应过度表达而导致的免疫病理反应,从而增强小鼠抵抗弓形虫感染的能力。

Objective To examine the immune mechanism by which lentinan （LTN） inhibits acute infection with Toxo- plasma gondii in mice through balancing of the Tht/Th2 immune response and maintaining that balance. Methods Mice were intraperitoneally injected with T. gondii tachyzoites and their survival rate was calculated when pre-treated with LTN and when treated with LTN post-infection. IFN-7 and IL 4 are key cytokines of Thl and Th2 cells, respective- ly. Levels of IFN-7 and 1L-4 in spleen cell suspensions were determined using ELISA. The immunoglobulins IgG1 and IgG2a are associated with Thl and Th2 response. Levels of these immunoglobulins in serum were also determined. Re- sults Lentinan markedly increased the survival rate {or mice treated with LTN post-injection and mice pre-treated with LTN in comparison to the control group. Mice treated with LTN post-infection all died on day 10 post infection, but mice pre-treated with LTN had a survival rate of 18.4% on day 13 post-infection. On day 3 post-infection, mice pre treated with LTN and mice treated with LTN post-infection had developed a Thl immune response. Mice pre-treated with LTN had an 1FN-7 level of 186.28 pg/ml while mice treated with LTN post-infection had an IFN-7 level of 117.07 pg/ml. There were significant differences in IFN 7 levels in comparison to the control group （P〈0.01）. Mice pre-treated with LTN had an IgG2a level of 0. 332（A490 ） while mice treated with LTN posbinfection had an IgG2a level of 0. 320（A490 ）（P 〈0.01）, and IgG2a levels peaked on day 7. Mice pre-treated with LTN and mice treated with LTN post-infection began to develop a Th2 immune response. Mice pre-treated with LTN had an IL-4 level of 121.28 pg/ml while mice treated with LTN post-infection had an IL-4 level of 94.47 pg/ml （P〈0.01）. Mice pre treated with LTN had an IgG1 level of 0. 382 （A490） and while mice treated with LTN post-infection had an IgG1 level of 0. 354（A490 ） （P〈0.05） . Conclusion LNT helped mice to develop a Thl/Th2 immune response. This balance shifted at the appropriate time from Thl to Th2, para- sites were eliminated, and the balance between the Thl and Th2 response was maintained. This avoided an excessive im- mune response as would induce immunopathological damage.