Toll-like receptor 9 mediates innate immune activation by the malaria pigment hemozoin.
Toll-like receptor 9 mediates innate immune activation by the malaria pigment hemozoin.
复制标题
Toll样受体9介导疟疾色素血液唑素的先天免疫激活。
DOI：
10.1084/jem.20041836
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发表时间：
2005-01-03
期刊：
影响因子：
--
通讯作者：
Akira S
中科院分区：
文献类型：
--
作者：
Coban C;Ishii KJ;Kawai T;Hemmi H;Sato S;Uematsu S;Yamamoto M;Takeuchi O;Itagaki S;Kumar N;Horii T;Akira S
红细胞内的疟原虫将宿主血红蛋白消化成疏水性血红素聚合物，称为疟原虫色素（HZ），随后释放到血流中，然后被网状内皮系统捕获并浓缩。越来越多的证据表明HZ具有免疫活性，但HZ调节先天免疫系统的分子机制尚未阐明。这项工作表明，从恶性疟原虫中纯化的HZ是一种新的Toll样受体（TLR）9的非DNA配体。HZ在体内和体外激活先天免疫应答，导致细胞因子、趋化因子的产生和共刺激分子的上调。这种反应在TLR 9 −/−和髓样分化因子88（MyD 88）−/−中严重受损，但在TLR 2、TLR 4、TLR 7或含有Toll/白细胞介素1受体结构域的衔接子诱导干扰素β−/−小鼠中没有。不含其他污染物的合成HZ也以TLR 9依赖性方式激活体内先天免疫应答。氯喹（CQ），一种抗疟疾药物，废除HZ诱导的细胞因子的产生。这些数据表明，TLR 9介导的，MyD 88依赖的，CQ敏感的先天免疫激活HZ可能在疟原虫-宿主相互作用中发挥重要作用。
Malaria parasites within red blood cells digest host hemoglobin into a hydrophobic heme polymer, known as hemozoin (HZ), which is subsequently released into the blood stream and then captured by and concentrated in the reticulo-endothelial system. Accumulating evidence suggests that HZ is immunologically active, but the molecular mechanism(s) through which HZ modulates the innate immune system has not been elucidated. This work demonstrates that HZ purified from Plasmodium falciparum is a novel non-DNA ligand for Toll-like receptor (TLR)9. HZ activated innate immune responses in vivo and in vitro, resulting in the production of cytokines, chemokines, and up-regulation of costimulatory molecules. Such responses were severely impaired in TLR9−/− and myeloid differentiation factor 88 (MyD88)−/−, but not in TLR2, TLR4, TLR7, or Toll/interleukin 1 receptor domain–containing adaptor-inducing interferon β−/− mice. Synthetic HZ, which is free of the other contaminants, also activated innate immune responses in vivo in a TLR9-dependent manner. Chloroquine (CQ), an antimalarial drug, abrogated HZ-induced cytokine production. These data suggest that TLR9-mediated, MyD88-dependent, and CQ-sensitive innate immune activation by HZ may play an important role in malaria parasite–host interactions.
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影响因子：
56.9
作者：
Yamamoto, M;Sato, S;Akira, S
通讯作者：
Akira, S
影响因子：
64.8
作者：
Hemmi, H;Takeuchi, O;Akira, S
通讯作者：
Akira, S
影响因子：
30.5
作者：
Latz, E;Schoenemeyer, A;Golenbock, DT
通讯作者：
Golenbock, DT
DOI：
10.1073/pnas.88.2.325
发表时间：
1991-01-01
影响因子：
11.1
作者：
SLATER, AFG;SWIGGARD, WJ;HENDERSON, GB
通讯作者：
HENDERSON, GB
影响因子：
4.4
作者：
Pichyangkul, S;Yongvanitchit, K;Hasegawa, H
通讯作者：
Hasegawa, H