Inhibitory role of toll-like receptors agonists in Plasmodium yoelii liver stage development
Inhibitory role of toll-like receptors agonists in Plasmodium yoelii liver stage development
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Toll 样受体激动剂对约氏疟原虫肝期发育的抑制作用
DOI：
10.1111/j.1365-3024.2009.01126.x
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发表时间：
2009-08-01
影响因子：
2.2
通讯作者：
Huang, F.
中科院分区：
文献类型：
--
作者：
Chen, J.;Xu, W.;Huang, F.
众所周知，先天免疫在控制疟原虫肝期发育过程中起着重要作用。然而，对Toll样受体（TLR）信号传导在红细胞前抗疟原虫免疫中的作用知之甚少。在此，我们发现用单个TLR激动剂pam 3CSK 4（TLR 2）、poly（I：C）（TLR 3）、LPS（TLR 4）和CpG（TLR 9）预处理可以显著降低小鼠中的肝疟原虫负荷，分别为58%、63%、75%和88%。此外，在用100个子孢子攻击的CpG组小鼠中，在14天内未观察到寄生虫血症。注射CpG前24 h，GdCl 3通过选择性抑制Kupffer细胞（KC）的吞噬能力，导致肝疟原虫负荷反弹，但不能完全中和CpG诱导的抗疟肝期免疫。与对照组相比，CpG预处理上调肝脏促炎细胞因子IL-12、IFN-γ和TNF-α，但下调抗炎细胞因子IL-10和TGF-β。因此，我们的数据表明，不同的TLR激动剂在疟原虫发育过程中的红细胞前期阶段的抑制作用。CpG作为最强的激动剂，可能通过调节肝内炎性细胞因子和增强KC细胞吞噬能力来抑制疟原虫肝期的发展。
It is well known that innate immune plays an important role in controlling the development of Plasmodium liver stage. However, little is known about the role of toll-like receptors (TLR) signalling in the pre-erythrocytic immunity against Plasmodium. Here, we found that pre-treatment with individual TLR agonist pam3CSK4 (TLR2), poly(I:C) (TLR3), LPS (TLR4) and CpG (TLR9) could decrease significantly the liver malaria parasite load in mice for 58%, 63%, 75% and 88% respectively. Moreover, no parasitaemia was observed within 14 days in CpG group mice challenged with 100 sporozoites. At 24 h prior to CpG injection, administration of gadolinium chloride (GdCl3) led to the rebound of liver Plasmodium load through inhibiting selectively Kupffer cells (KC) phagocytosis capacity but failed to neutralize completely CpG-induced immunity against malaria liver stage. Compared with the control, pre-treatment of CpG up-regulated hepatic pro-inflammatory cytokines IL-12, IFN-gamma and TNF-alpha, but down-regulated anti-inflammatory cytokines IL-10 and TGF-beta. Hence, our data demonstrated the inhibitory role of diverse TLR agonists in the Plasmodium development during pre-erythrocytic stage. As the most robust agonist, CpG might inhibit the development of Plasmodium liver stage through regulation of intrahepatic inflammatory cytokines and enhancement of KC cells phagocytosis capacity.