MicroRNA and mRNA Transcriptome Profiling in Primary Human Astrocytes Infected with Borrelia burgdorferi
MicroRNA and mRNA Transcriptome Profiling in Primary Human Astrocytes Infected with Borrelia burgdorferi
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DOI：
10.1371/journal.pone.0170961
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发表时间：
2017-01-30
期刊：
影响因子：
3.7
通讯作者：
Brissette, Catherine A.
中科院分区：
文献类型：
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作者：
Casselli, Timothy;Qureshi, Humaira;Brissette, Catherine A.
莱姆病是由感染伯氏疏螺旋体（Bb）引起的，该细菌通过鹿蜱传播给人类。感染通常表现为皮疹和轻微的全身症状;然而，细菌可以扩散到其他组织，引起关节疼痛，心脏炎和神经系统症状。莱姆神经疏螺旋体病以几种方式呈现，例如贝尔麻痹，脑膜炎和脑炎。神经疏螺旋体病的分子基础知之甚少。因此，分析Bb感染后信使RNA和非编码RNA（包括microRNA）表达水平的变化可以提供有关神经疏螺旋体病发病机制和临床症状的重要信息。为此，我们使用培养的原代人星形胶质细胞，CNS感染的关键反应者和血脑屏障的重要组成部分，作为研究Bb引起的CNS中RNA和microRNA变化的模型系统。使用全转录组RNA-seq，我们发现在Bb感染后24和48小时，38种microRNA和275种mRNA发生了显著变化。一些RNA变化影响参与免疫应答、发育、染色质组装（包括组蛋白）和细胞粘附的途径。此外，几种microRNA预测的靶mRNA也受到差异调节。总的来说，我们的研究结果表明，暴露于Bb会导致星形胶质细胞的转录组和microRNA谱发生显著变化，这对发病机制有影响，因此可能有治疗这种疾病的策略。
Lyme disease is caused by infection with the bacterium Borrelia burgdorferi (Bb), which is transmitted to humans by deer ticks. The infection manifests usually as a rash and minor systemic symptoms; however, the bacteria can spread to other tissues, causing joint pain, carditis, and neurological symptoms. Lyme neuroborreliosis presents itself in several ways, such as Bell's palsy, meningitis, and encephalitis. The molecular basis for neuroborreliosis is poorly understood. Analysis of the changes in the expression levels of messenger RNAs and non-coding RNAs, including microRNAs, following Bb infection could therefore provide vital information on the pathogenesis and clinical symptoms of neuroborreliosis. To this end, we used cultured primary human astrocytes, key responders to CNS infection and important components of the blood-brain barrier, as a model system to study RNA and microRNA changes in the CNS caused by Bb. Using whole transcriptome RNA-seq, we found significant changes in 38 microRNAs and 275 mRNAs at 24 and 48 hours following Bb infection. Several of the RNA changes affect pathways involved in immune response, development, chromatin assembly (including histones) and cell adhesion. Further, several of the microRNA predicted target mRNAs were also differentially regulated. Overall, our results indicate that exposure to Bb causes significant changes to the transcriptome and microRNA profile of astrocytes, which has implications in the pathogenesis, and hence potential treatment strategies to combat this disease.