Department of Immunology, College of Basic Medical Sciences, China Medical University, No,92, Bei'er Road, Heping District, Shenyang, Liaoning 110001, China.
Malar J. 2012 Feb 20;11:49. doi: 10.1186/1475-2875-11-49.
Clinical immunity to malaria in human populations is developed after repeated exposure to malaria. Regulation and balance of host immune responses may lead to optimal immunity against malaria parasite infection. Polysaccharides (ABPS) derived from the Chinese herb ox knee Achyranthes bidentata possess immuno-modulatory functions. The aim of this study is to use the rodent malaria model Plasmodium yoelii 17XL (P. y17XL) to examine whether pretreatment with ABPS will modulate host immunity against malaria infection and improve the outcome of the disease.
To determine whether ABPS could modulate immunity against malaria, mice were pretreated with ABPS prior to blood-stage infection by P. y17XL. Host survival and parasitaemia were monitored daily. The effect of pretreatment on host immune responses was studied through the quantitation of cytokines, dendritic cell populations, and natural regulatory T cells (Treg).
Pretreatment with ABPS prior to infection significantly extended the survival time of mice after P. y17XL infection. At three and five days post-infection, ABPS pretreated mice developed stronger Th1 immune responses against malaria infection with the number of F4/80+CD36+ macrophages and levels of IFN-γ, TNF-α and nitric oxide being significantly higher than in the control group. More importantly, ABPS-treated mice developed more myeloid (CD11c+CD11b+) and plasmacytoid dendritic cells (CD11c+CD45R+/B220+) than control mice. ABPS pretreatment also resulted in modulated expression of MHC-II, CD86, and especially Toll-like receptor 9 by CD11c+ dendritic cells. In comparison, pretreatment with ABPS did not alter the number of natural Treg or the production of the anti-inflammatory cytokine IL-10.
Pretreatment with the immuno-modulatory ABPS selectively enhanced Th1 immune responses to control the proliferation of malaria parasites, and prolonged the survival of mice during subsequent malaria infection.
人类群体对疟疾的临床免疫力是在反复接触疟疾后产生的。宿主免疫反应的调节和平衡可能导致对疟原虫感染的最佳免疫。从中药牛膝 Achyranthes bidentata 中提取的多糖（ABPS）具有免疫调节功能。本研究旨在使用啮齿动物疟疾模型 Plasmodium yoelii 17XL（P.y17XL）来检查 ABPS 预处理是否会调节宿主对疟疾感染的免疫反应并改善疾病的结果。
为了确定 ABPS 是否可以调节对疟疾的免疫力，在 P.y17XL 血期感染前用 ABPS 预处理小鼠。每天监测宿主存活率和寄生虫血症。通过定量细胞因子、树突状细胞群体和天然调节性 T 细胞（Treg）来研究预处理对宿主免疫反应的影响。
感染前用 ABPS 预处理可显著延长 P.y17XL 感染后小鼠的存活时间。在感染后第 3 天和第 5 天，ABPS 预处理的小鼠对疟疾感染产生了更强的 Th1 免疫反应，F4/80+CD36+巨噬细胞数量以及 IFN-γ、TNF-α 和一氧化氮水平明显高于对照组。更重要的是，ABPS 处理的小鼠比对照组小鼠产生了更多的髓样（CD11c+CD11b+）和浆细胞样树突状细胞（CD11c+CD45R+/B220+）。ABPS 预处理还导致 CD11c+树突状细胞中 MHC-II、CD86 和特别是 Toll 样受体 9 的表达发生调节。相比之下，ABPS 预处理并未改变天然 Treg 的数量或抗炎细胞因子 IL-10 的产生。
用免疫调节 ABPS 预处理可选择性增强 Th1 免疫反应，以控制疟原虫的增殖，并在随后的疟疾感染中延长小鼠的存活时间。
