Exosomal RNA from Mycobacterium tuberculosis-Infected Cells Is Functional in Recipient Macrophages.
Exosomal RNA from Mycobacterium tuberculosis-Infected Cells Is Functional in Recipient Macrophages.
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DOI：
10.1111/tra.12278
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发表时间：
2015-06
期刊：
影响因子：
--
通讯作者：
Schorey JS
中科院分区：
文献类型：
--
作者：
Singh PP;Li L;Schorey JS
胞外体是细胞释放的胞外小泡，携带蛋白质、脂类和核酸，在细胞间通讯中发挥作用。在此之前，我们确定结核分枝杆菌感染的巨噬细胞释放的外切体携带分枝杆菌蛋白和脂类。然而，这些外切体中的RNA组成还没有确定。在这项研究中，我们对结核分枝杆菌感染的巨噬细胞释放的外切体进行了表征，并鉴定了一组小鼠的mRNA和miRNA。定量RT-PCR分析显示，与未感染的巨噬细胞相比，感染的巨噬细胞释放的外切体中miRNAs的丰度较低。此外，超过100个转录本被发现是来自感染细胞的外切体的丰富或独特的，包括参与调节免疫反应的转录本。外体RNA可以在幼稚的巨噬细胞中转移和表达，具有生物活性，刺激炎性介质的产生，并诱导受体细胞的凋亡。有趣的是，我们还在受感染的巨噬细胞释放的外体以及从结核病患者血清中分离的外体中发现了分枝杆菌转录本。据我们所知，这是第一次在外切体中鉴定细菌衍生的RNA的研究。我们的结果表明，结核分枝杆菌感染的巨噬细胞释放的外体RNA在分枝杆菌感染的背景下可能具有功能和诊断潜力。
Exosomes are extracellular vesicles released by cells which carry proteins, lipids and nucleic acids and function in intercellular communication. Previously we determined that exosomes released from Mycobacterium tuberculosis infected macrophages carry mycobacterial proteins and lipids. However, the RNA composition within these exosomes has not been defined. In this study we characterized the exosomes released from M .tuberculosis-infected macrophages and identified a cohort of mouse mRNA and miRNA. Quantitative RT-PCR analysis showed less abundance of miRNAs in exosomes released from infected compared to uninfected macrophages. Moreover, over 100 transcripts were found to be enriched or unique to exosomes from infected cells including transcripts involved in regulating an immune response. The exosomal RNA could be transferred and expressed in naïve macrophages and was biological active, stimulating production of inflammatory mediators and inducing apoptosis in recipient cells. Interestingly, we also identified mycobacterial transcripts in exosomes released from infected macrophages as well as from exosomes isolated from TB patient serum. To our knowledge this is the first study to identify bacterial-derived RNA in exosomes. Our results suggest that exosomal RNA released from M. tuberculosis-infected macrophages may have functional and diagnostic potential in the context of a mycobacterial infection.
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影响因子：
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作者：
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