Malaria parasites require TLR9 signaling for immune evasion by activating regulatory T cells.
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.
Hisaeda
Hajime
H
Department of Parasitology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Japan. hisa@parasite.med.kyushu-u.ac.jp
Tetsutani
Kohhei
K
Imai
Takashi
T
Moriya
Chikako
C
Tu
Liping
L
Hamano
Shinjiro
S
Duan
Xuefeng
X
Chou
Bin
B
Ishida
Hidekazu
H
Aramaki
Akiko
A
Shen
Jianying
J
Ishii
Ken J
KJ
Coban
Cevayir
C
Akira
Shizuo
S
Takeda
Kiyoshi
K
Yasutomo
Koji
K
Torii
Motomi
M
Himeno
Kunisuke
K
D000818:Animals; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D006790:Host-Parasite Interactions / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D008288:Malaria / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010967:Plasmodium yoelii / Q000276:immunology* / Q000472:pathogenicity; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology*; D051217:Toll-Like Receptor 9 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
C495370:Tlr9 protein, mouse; D051217:Toll-Like Receptor 9