Plasmodium falciparum-derived uric acid precipitates induce maturation of dendritic cells.
Plasmodium falciparum-derived uric acid precipitates induce maturation of dendritic cells.
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DOI：
10.1371/journal.pone.0055584
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Rodriguez A
中科院分区：
文献类型：
--
作者：
van de Hoef DL;Coppens I;Holowka T;Ben Mamoun C;Branch O;Rodriguez A
疟疾的特点是周期性发烧和高度炎症，虽然早期的炎症反应有助于清除寄生虫，但过度和持续的炎症可导致疾病的严重形式。在这里，我们发现恶性疟原虫感染的红细胞在寄生液泡的细胞质中含有尿酸沉淀，当红细胞破裂时释放尿酸沉淀。尿酸沉淀物是高度炎症分子，被认为是先天免疫的危险信号，是痛风的病原体。我们确定恶性疟原虫衍生的尿酸沉淀物诱导人树突状细胞成熟，增加细胞表面共刺激分子如CD80和CD86的表达，同时降低人白细胞抗原- dr的表达。由此可见，尿酸在被寄生虫感染的红细胞诱导的总刺激活性中占相当大的比例。此外，在直接从疟疾患者获得的恶性疟原虫和间日疟原虫感染的红细胞中鉴定尿酸沉淀，强调了我们研究结果的体内和临床相关性。总之，我们的数据表明尿酸沉淀物对疟原虫感染的先天免疫反应具有潜在的重要作用，并可能为辅助治疗提供新的靶点。
Malaria is characterized by cyclical fevers and high levels of inflammation, and while an early inflammatory response contributes to parasite clearance, excessive and persistent inflammation can lead to severe forms of the disease. Here, we show that Plasmodium falciparum-infected erythrocytes contain uric acid precipitates in the cytoplasm of the parasitophorous vacuole, which are released when erythrocytes rupture. Uric acid precipitates are highly inflammatory molecules that are considered a danger signal for innate immunity and are the causative agent in gout. We determined that P. falciparum-derived uric acid precipitates induce maturation of human dendritic cells, increasing the expression of cell surface co-stimulatory molecules such as CD80 and CD86, while decreasing human leukocyte antigen-DR expression. In accordance with this, uric acid accounts for a significant proportion of the total stimulatory activity induced by parasite-infected erythrocytes. Moreover, the identification of uric acid precipitates in P. falciparum- and P. vivax-infected erythrocytes obtained directly from malaria patients underscores the in vivo and clinical relevance of our findings. Altogether, our data implicate uric acid precipitates as a potentially important contributor to the innate immune response to Plasmodium infection and may provide a novel target for adjunct therapies.
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DOI：
10.3923/pjbs.2008.1646.1649
发表时间：
2008-06-15
期刊：
Pakistan journal of biological sciences : PJBS
影响因子：
--
作者：
Bertrand, Kouam Eric;Mathieu, Ndomou;Honore, Fotso Kuate
通讯作者：
Honore, Fotso Kuate
影响因子：
2
作者：
Iwama, Mizuki;Kondo, Yoshitaka;Ishigami, Akihito
通讯作者：
Ishigami, Akihito
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：
4.9
作者：
Busso N;So A
通讯作者：
So A
影响因子：
2.9
作者：
BOULIEU, R;BORY, C;GONNET, C
通讯作者：
GONNET, C