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Hajime Hisaeda, Kohhei Tetsutani, Takashi Imai, Chikako Moriya, Liping Tu, Shinjiro Hamano, Xuefeng Duan, Bin Chou, Hidekazu Ishida, Akiko Aramaki, Jianying Shen, Ken J Ishii, Cevayir Coban, Shizuo Akira, Kiyoshi Takeda, Koji Yasutomo, Motomi Torii, Kunisuke Himeno, Malaria Parasites Require TLR9 Signaling for Immune Evasion by Activating Regulatory T Cells, The Journal of Immunology, Volume 180, Issue 4, February 2008, Pages 2496–2503, https://doi.org/10.4049/jimmunol.180.4.2496
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Abstract
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.