Department of Medical Parasitology, New York University School of Medicine, 341 East 25th street, New York, NY 10010, USA.
Malar J. 2010 Mar 1;9:64. doi: 10.1186/1475-2875-9-64.
Infection with Plasmodium is the cause of malaria, a disease characterized by a high inflammatory response in the blood. Dendritic cells (DC) participate in both adaptive and innate immune responses, influencing the generation of inflammatory responses. DC can be activated through different receptors, which recognize specific molecules in microbes and induce the maturation of DC.
Using Plasmodium yoelii, a rodent malaria model, the effect of Plasmodium-infected erythrocytes on DC maturation and TLR responses have been analysed.
It was found that intact erythrocytes infected with P. yoelii do not induce maturation of DC unless they are lysed, suggesting that accessibility of parasite inflammatory molecules to their receptors is a key issue in the activation of DC by P. yoelii. This activation is independent of MyD88. It was also observed that pre-incubation of DC with intact P. yoelii-infected erythrocytes inhibits the maturation response of DC to other TLR stimuli. The inhibition of maturation of DC is reversible, parasite-specific and increases with the stage of parasite development, with complete inhibition induced by schizonts (mature infected erythrocytes). Plasmodium yoelii-infected erythrocytes induce a broad inhibitory effect rendering DC non-responsive to ligands for TLR2, TLR3, TLR4, TLR5, TLR7 and TLR9.
Despite the presence of inflammatory molecules within Plasmodium-infected erythrocytes, which are probably responsible for DC maturation induced by lysates, intact Plasmodium-infected erythrocytes induce a general inhibition of TLR responsiveness in DC. The observed effect on DC could play an important role in the pathology and suboptimal immune response observed during the disease. These results help to explain why immune functions are altered during malaria, and provide a system for the identification of a parasite-derived broad inhibitor of TLR-mediated signaling pathways.
疟原虫感染是疟疾的病因，这种疾病的特点是血液中存在强烈的炎症反应。树突状细胞（DC）参与适应性和固有免疫反应，影响炎症反应的发生。DC 可以通过不同的受体被激活，这些受体识别微生物中的特定分子并诱导 DC 的成熟。
利用鼠疟原虫 Plasmodium yoelii 模型，分析了疟原虫感染的红细胞对 DC 成熟和 TLR 反应的影响。
研究发现，未被裂解的完整疟原虫感染红细胞不会诱导 DC 成熟，这表明寄生虫炎症分子与受体的可及性是疟原虫激活 DC 的关键问题。这种激活不依赖于 MyD88。还观察到，DC 与完整的 Plasmodium yoelii 感染的红细胞预孵育会抑制 DC 对其他 TLR 刺激物的成熟反应。DC 成熟的抑制是可逆的、寄生虫特异性的，并随着寄生虫发育阶段的增加而增加，裂殖体（成熟的感染红细胞）可诱导完全抑制。疟原虫感染的红细胞诱导广泛的抑制作用，使 DC 对 TLR2、TLR3、TLR4、TLR5、TLR7 和 TLR9 的配体无反应。
尽管疟原虫感染的红细胞中存在可能导致裂解物诱导 DC 成熟的炎症分子，但完整的疟原虫感染的红细胞会诱导 DC 对 TLR 反应性的普遍抑制。在 DC 中观察到的这种效应可能在疾病期间观察到的病理和免疫反应不佳中发挥重要作用。这些结果有助于解释为什么免疫功能在疟疾期间发生改变，并提供了一个鉴定寄生虫衍生的 TLR 介导信号通路广泛抑制剂的系统。
