Malaria parasites require TLR9 signaling for immune evasion by activating regulatory T cells
Malaria parasites require TLR9 signaling for immune evasion by activating regulatory T cells
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DOI：
10.4049/jimmunol.180.4.2496
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发表时间：
2008-02-15
影响因子：
4.4
通讯作者：
Himeno, Kunisuke
中科院分区：
文献类型：
--
作者：
Hisaeda, Hajime;Tetsutani, Kohhei;Himeno, Kunisuke
疟疾仍然是一种威胁生命的传染病，每年继续造成200万人死亡。疟疾寄生虫具有获得性免疫逃逸机制并阻止不育免疫的发展。据报道，调节性T细胞（TCRs）有助于小鼠和人类疟疾期间的免疫逃避，这表明激活TCRs是疟疾寄生虫破坏宿主免疫系统的机制之一。然而，人们对这些寄生虫如何激活TdR知之甚少。我们在此表明，TLR 9信号传导到树突状细胞（DC）是至关重要的激活TCLs。小鼠感染约氏疟原虫后会激活Teptide，从而增强其抑制功能。体外活化TCLs需要DC以TLR 9依赖性方式与寄生虫相互作用。此外，TLR 9（-/-）小鼠对致死性感染具有部分抗性，并且这与受损的T细胞活化和随后的效应T细胞发育有关。因此，疟疾寄生虫需要TLR 9来激活Tcl 3以进行免疫逃逸。
Malaria is still a life-threatening infectious disease that continues to produce 2 million deaths annually. Malaria parasites have acquired immune escape mechanisms and prevent the development of sterile immunity. Regulatory T cells (Tregs) have been reported to contribute to immune evasion during malaria in mice and humans, suggesting that activating Tregs is one of the mechanisms by which malaria parasites subvert host immune systems. However, little is known about how these parasites activate Tregs. We herein show that TLR9 signaling to dendritic cells (DCs) is crucial for activation of Tregs. Infection of mice with the rodent malaria parasite Plasmodium yoelii activates Tregs, leading to enhancement of their suppressive function. In vitro activation of Tregs requires the interaction of DCs with parasites in a TLR9-dependent manner. Furthermore, TLR9(-/-) mice are partially resistant to lethal infection, and this is associated with impaired activation of Tregs and subsequent development of effector T cells. Thus, malaria parasites require TLR9 to activate Tregs for immune escape.