Malaria-infected erythrocyte-derived microvesicles mediate cellular communication within the parasite population and with the host immune system.

Malaria-infected erythrocyte-derived microvesicles mediate cellular communication within the parasite population and with the host immune system.
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DOI:
10.1016/j.chom.2013.04.009
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发表时间:
2013-05-15
影响因子:
30.3
通讯作者:
Marti M
Marti M
中科院分区:
医学1区
文献类型:
--
作者:
Mantel PY;Hoang AN;Goldowitz I;Potashnikova D;Hamza B;Vorobjev I;Ghiran I;Toner M;Irimia D;Ivanov AR;Barteneva N;Marti M

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已知感染不同疟原虫株的人和小鼠产生源自感染的红细胞(RBC)的微泡,表示为RMV。在小鼠中的研究表明,RMV在感染期间升高,并具有促炎活性。在这里,我们提出了一个详细的RMV的组成和功能在人类疟疾寄生虫恶性疟原虫的特性。蛋白质组学分析揭示了多种宿主和寄生虫蛋白质的富集,特别是与宿主细胞膜相关的寄生虫抗原和寄生虫侵入RBC的蛋白质。在寄生虫排出之前,在无性寄生虫周期期间定量释放RMV。RMV对人原代巨噬细胞和中性粒细胞表现出强效免疫调节特性。此外,RMV被感染的红细胞内化,并以剂量依赖性方式刺激传播阶段寄生虫的产生。因此,RMV介导寄生虫群体内以及与宿主先天免疫系统的细胞通讯。
Humans and mice infected with different Plasmodium strains are known to produce microvesicles derived from the infected red blood cells (RBC), denoted RMVs. Studies in mice have shown that RMVs are elevated during infection and have pro-inflammatory activity. Here we present a detailed characterization of RMV composition and function in the human malaria parasite Plasmodium falciparum. Proteomics profiling revealed the enrichment of multiple host and parasite proteins, in particular of parasite antigens associated with host cell membranes and proteins involved in parasite invasion into RBCs. RMVs are quantitatively released during the asexual parasite cycle prior to parasite egress. RMVs demonstrate potent immunomodulatory properties on human primary macrophages and neutrophils. Additionally, RMVs are internalized by infected red blood cells and stimulate production of transmission stage parasites in a dose-dependent manner. Thus, RMVs mediate cellular communication within the parasite population and with the host innate immune system.
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