Infected erythrocyte-derived extracellular vesicles alter vascular function via regulatory Ago2-miRNA complexes in malaria.
Infected erythrocyte-derived extracellular vesicles alter vascular function via regulatory Ago2-miRNA complexes in malaria.
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DOI：
10.1038/ncomms12727
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发表时间：
2016-10-10
影响因子：
16.6
通讯作者：
Marti M
中科院分区：
文献类型：
--
作者：
Mantel PY;Hjelmqvist D;Walch M;Kharoubi-Hess S;Nilsson S;Ravel D;Ribeiro M;Grüring C;Ma S;Padmanabhan P;Trachtenberg A;Ankarklev J;Brancucci NM;Huttenhower C;Duraisingh MT;Ghiran I;Kuo WP;Filgueira L;Martinelli R;Marti M
疟疾仍然是世界上最大的公共卫生挑战之一，特别是在撒哈拉以南非洲。恶性疟原虫感染个体的临床预后取决于多种因素，包括宿主全身炎症反应、组织中寄生虫的隔离和血管功能障碍。促炎细胞因子和趋化因子的产生促进了内皮细胞的激活以及炎症细胞的募集和浸润，这反过来又触发了内皮细胞的进一步激活和寄生虫的隔离。炎症反应部分是由生物活性寄生虫产物如血色素和受感染的红细胞衍生的细胞外囊泡（irbc衍生的EVs）引发的。在这里，我们证明这些ev含有来自宿主红细胞的功能性miRNA-Argonaute 2复合物。此外，我们发现内皮细胞可以有效地内化ev，其中miRNA-Argonaute 2复合物调节靶基因表达和屏障特性。总之，这些发现提供了EVs与疟疾感染期间血管功能障碍之间的机制联系。对疟疾病原体恶性疟原虫的炎症反应可由受感染的红细胞来源的细胞外囊泡（EVs）触发。该研究表明，这些ev含有功能microRNA-Argonaute 2复合物，可调节基因表达并改变血管屏障特性。
Malaria remains one of the greatest public health challenges worldwide, particularly in sub-Saharan Africa. The clinical outcome of individuals infected with Plasmodium falciparum parasites depends on many factors including host systemic inflammatory responses, parasite sequestration in tissues and vascular dysfunction. Production of pro-inflammatory cytokines and chemokines promotes endothelial activation as well as recruitment and infiltration of inflammatory cells, which in turn triggers further endothelial cell activation and parasite sequestration. Inflammatory responses are triggered in part by bioactive parasite products such as hemozoin and infected red blood cell-derived extracellular vesicles (iRBC-derived EVs). Here we demonstrate that such EVs contain functional miRNA-Argonaute 2 complexes that are derived from the host RBC. Moreover, we show that EVs are efficiently internalized by endothelial cells, where the miRNA-Argonaute 2 complexes modulate target gene expression and barrier properties. Altogether, these findings provide a mechanistic link between EVs and vascular dysfunction during malaria infection. Inflammatory response to malaria pathogen Plasmodium falciparum can be triggered by infected red blood cell-derived extracellular vesicles (EVs). This study shows these EVs contain functional microRNA-Argonaute 2 complex that modulates gene expression and alter vascular barrier properties.
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DOI：
10.1073/pnas.0400195101
发表时间：
2004-03-23
影响因子：
11.1
作者：
Bhoumik, A;Jones, N;Ronai, Z
通讯作者：
Ronai, Z
影响因子：
4.1
作者：
Jackson, Katherine E.;Spielmann, Tobias;Tilley, Leann
通讯作者：
Tilley, Leann
DOI：
10.1126/science.1190809
发表时间：
2010-06-25
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Cifuentes D;Xue H;Taylor DW;Patnode H;Mishima Y;Cheloufi S;Ma E;Mane S;Hannon GJ;Lawson ND;Wolfe SA;Giraldez AJ
通讯作者：
Giraldez AJ
影响因子：
5.1
作者：
Alves, M. P.;Neuhaus, V.;Summerfield, A.
通讯作者：
Summerfield, A.
影响因子：
20.3
作者：
Barres, Celine;Blanc, Lionel;Vidal, Michel
通讯作者：
Vidal, Michel