The nucleosome (histone-DNA complex) is the TLR9-specific immunostimulatory component of Plasmodium falciparum that activates DCs.
The nucleosome (histone-DNA complex) is the TLR9-specific immunostimulatory component of Plasmodium falciparum that activates DCs.
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DOI：
10.1371/journal.pone.0020398
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Gowda DC
中科院分区：
文献类型：
--
作者：
Gowda NM;Wu X;Gowda DC
恶性疟原虫感染的全身临床症状，如发热和寒战，对应于裂殖体同步破裂时释放的寄生虫成分所产生的促炎细胞因子。我们最近证实，在裂殖体释放的产物中，裂殖子是通过TLR9特异性识别激活树突状细胞(DC)、诱导细胞成熟和产生促炎细胞因子的主要成分。我们还证明了DNA是活性成分，DNA-蛋白质复合体的形成对于寄生虫DNA进入细胞以供TLR9识别是必不可少的。然而，寄生虫内源性蛋白质-DNA复合体的性质尚不清楚。在这项研究中，我们证明了寄生虫核小体是参与寄生虫核物质激活DC的主要蛋白质-DNA复合体。寄生虫成分被分成核物质和非核物质。核物质进一步分离成染色质，蛋白质松散地结合到染色质上。从染色质中制备多核小体和寡核小体。检测它们对来自野生型、TLR2−/−、TLR9−/−和MyD88−/−小鼠的骨髓细胞通过Flt3配体分化获得的DC的激活能力。核小体和多核小体以及单核小体和寡核小体刺激的DC以TLR9依赖的方式有效地诱导促炎细胞因子的产生，表明核小体(组蛋白-DNA复合体)是疟疾寄生虫核材料中主要的TLR9特异性DC免疫刺激成分。因此，我们的数据为疟疾寄生虫激活DC提供了重要的洞察力，并对疟疾疫苗的开发具有重要意义。
The systemic clinical symptoms of Plasmodium falciparum infection such as fever and chills correspond to the proinflammatory cytokines produced in response to the parasite components released during the synchronized rupture of schizonts. We recently demonstrated that, among the schizont-released products, merozoites are the predominant components that activate dendritic cells (DCs) by TLR9-specific recognition to induce the maturation of cells and to produce proinflammatory cytokines. We also demonstrated that DNA is the active constituent and that formation of a DNA-protein complex is essential for the entry of parasite DNA into cells for recognition by TLR9. However, the nature of endogenous protein-DNA complex in the parasite is not known. In this study, we show that parasite nucleosome constitute the major protein-DNA complex involved in the activation of DCs by parasite nuclear material. The parasite components were fractionated into the nuclear and non-nuclear materials. The nuclear material was further fractionated into chromatin and the proteins loosely bound to chromatin. Polynucleosomes and oligonucleosomes were prepared from the chromatin. These were tested for their ability to activate DCs obtained by the FLT3 ligand differentiation of bone marrow cells from the wild type, and TLR2−/−, TLR9−/− and MyD88−/− mice. DCs stimulated with the nuclear material and polynucleosomes as well as mono- and oligonucleosomes efficiently induced the production of proinflammatory cytokines in a TLR9-dependent manner, demonstrating that nucleosomes (histone-DNA complex) represent the major TLR9-specific DC-immunostimulatory component of the malaria parasite nuclear material. Thus, our data provide a significant insight into the activation of DCs by malaria parasites and have important implications for malaria vaccine development.
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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
发表时间：
2005-01-03
期刊：
The Journal of experimental medicine
影响因子：
--
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
通讯作者：
Akira S
影响因子：
4.4
作者：
Foureau, David M.;Mielcarz, Daniel W.;Buzoni-Gatel, Dominique
通讯作者：
Buzoni-Gatel, Dominique
影响因子：
4.4
作者：
Bartholomeu, Daniella C.;Ropert, Catherine;Gazzinelli, Ricardo T.
通讯作者：
Gazzinelli, Ricardo T.
影响因子：
5.5
作者：
de Alencar, Bruna C. G.;Araujo, Adriano F. S.;Rodrigues, Mauricio M.
通讯作者：
Rodrigues, Mauricio M.
影响因子：
4.8
作者：
Alkhalil, A;Achur, RN;Gowda, DC
通讯作者：
Gowda, DC