Toll-like receptor 4, Toll-like receptor 7 and Toll-like receptor 9 agonists enhance immune responses against blood-stage Plasmodium chabaudi infection in BALB/c mice
Toll-like receptor 4, Toll-like receptor 7 and Toll-like receptor 9 agonists enhance immune responses against blood-stage Plasmodium chabaudi infection in BALB/c mice
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Toll 样受体 4、Toll 样受体 7 和 Toll 样受体 9 激动剂增强 BALB/c 小鼠针对血期恰鲍迪疟原虫感染的免疫反应
DOI：
10.1016/j.intimp.2020.107096
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发表时间：
2020
影响因子：
5.6
通讯作者：
Cao Yaming
中科院分区：
文献类型：
--
作者：
Gao Wenyan;Sun Xiaodan;Li Danni;Sun Lin;He Yang;Wei Huanping;Jin Feng;Cao Yaming
背景：Toll样受体（TLR）信号在疟疾感染的血液阶段起着至关重要的作用。然而，TLR激动剂在调节免疫应答和发展对疟疾的保护性免疫中的作用仍然知之甚少。方法：BALB/c小鼠经TLR 4、TLR 7和TLR 9激动剂预处理后，感染夏氏疟原虫。感染后，用流式细胞仪检测脾脏树突状细胞（DC）、Th 1细胞、Th 1细胞上表达的程序性死亡-1（PD-1）以及调节性T细胞（TCR）。通过ELISA测定脾细胞中IFN-γ、TNF-α、TGF-β和IL-10以及血清中IgG 1和IgG 2a的水平。结果：感染前给予TLR 4、TLR 7和TLR 9激动剂可改善疾病结局。所有TLR激动剂促进DC活化，并且Th 1细胞的比例增加。在TLR 4、TLR 7和TLR 9激动剂治疗组中，促炎细胞因子IFN-γ和TNF-α的水平升高，并且IgG 1和IgG 2a血清水平也显著升高。TLR 4、TLR 7和TLR 9激动剂减少了Tcl 3的活化，并下调了抗炎细胞因子TGF-β和IL-10。最后，与对照组相比，TLR 4、TLR 7和TLR 9激动剂处理组中Th 1细胞上表达的PD-1减少。结论：TLR 4、TLR 7和TLR 9激动剂可激活DC介导的天然免疫应答和适应性免疫应答，从而对抗疟原虫的血液期，有望应用于疟疾的预防和治疗。
Background: Toll-like receptor (TLR) signals play vital roles during the blood-stage of malaria infections. However, the roles of TLR agonists in the regulation of immune responses and the development of protective immunity to malaria remain poorly understood. Method: BALB/c mice were pre-treated with TLR4, TLR7 and TLR9 agonists, followed by infection with Plasmodium chabaudi. After infection, splenic dendritic cells (DCs), Th1 cells and programmed death-1 (PD-1) expressed on Th1 cells, as well as regulatory T cells (Tregs) were analyzed by flow cytometry. The levels of IFN-gamma, TNF-alpha, TGF-beta and IL-10 in splenocytes and IgG1 and IgG2a in serum were measured by ELISA. Result: Administration of TLR4, TLR7 and TLR9 agonists prior to infection improved disease outcomes. All TLR agonists promoted DC activation, and the proportions of Th1 cells increased. In TLR4, TLR7 and TLR9 agonist treated groups the levels of pro-inflammatory cytokines IFN-gamma and TNF-alpha were elevated, and IgG1 and IgG2a serum levels were also significantly increased. TLR4, TLR7 and TLR9 agonists diminished the activation of Tregs and down-regulated the anti-inflammatory cytokines TGF-beta and IL-10. Finally, PD-1 expressed on Th1 cells were decreased in TLR4, TLR7 and TLR9 agonist treated groups compared with control groups. Conclusion: TLR4, TLR7 and TLR9 agonists activated DC-mediated innate immune responses and adaptive immune response, which against the blood-stage of Plasmodium and might be applied to malaria protection and treatment.