title: Malaria parasites require TLR9 signaling for immune evasion by activating regulatory T cells.
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.
authors.affiliation: 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
authors.forename: Hajime
authors.initials: H
authors.lastname: Hisaeda
authors.forename: Kohhei
authors.initials: K
authors.lastname: Tetsutani
authors.forename: Takashi
authors.initials: T
authors.lastname: Imai
authors.forename: Chikako
authors.initials: C
authors.lastname: Moriya
authors.forename: Liping
authors.initials: L
authors.lastname: Tu
authors.forename: Shinjiro
authors.initials: S
authors.lastname: Hamano
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Duan
authors.forename: Bin
authors.initials: B
authors.lastname: Chou
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Ishida
authors.forename: Akiko
authors.initials: A
authors.lastname: Aramaki
authors.forename: Jianying
authors.initials: J
authors.lastname: Shen
authors.forename: Ken J
authors.initials: KJ
authors.lastname: Ishii
authors.forename: Cevayir
authors.initials: C
authors.lastname: Coban
authors.forename: Shizuo
authors.initials: S
authors.lastname: Akira
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Takeda
authors.forename: Koji
authors.initials: K
authors.lastname: Yasutomo
authors.forename: Motomi
authors.initials: M
authors.lastname: Torii
authors.forename: Kunisuke
authors.initials: K
authors.lastname: Himeno
mesh_terms: 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*
chemical_list: C495370:Tlr9 protein, mouse; D051217:Toll-Like Receptor 9