Transcriptionally induced enhancers in the macrophage immune response to Mycobacterium tuberculosis infection
Transcriptionally induced enhancers in the macrophage immune response to Mycobacterium tuberculosis infection
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DOI：
10.1186/s12864-019-5450-6
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发表时间：
2019-01-22
期刊：
影响因子：
4.4
通讯作者：
Schmeier, Sebastian
中科院分区：
文献类型：
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作者：
Denisenko, Elena;Guler, Reto;Schmeier, Sebastian
背景结核病是由结核分枝杆菌（Mycobacterium tuberculosis，M.tb）引起的一种严重威胁人类生命的传染病。结核分枝杆菌破坏宿主免疫反应，以建立有利的生态位并在宿主巨噬细胞内存活。如果获得适当的功能表型，巨噬细胞可以控制或消除感染。转录调控是控制这些表型的激活和维持的关键过程。在结核分枝杆菌感染过程中的转录调控因素编排，转录增强子仍然是unexplored.ResultsWe分析转录增强子结核分枝杆菌感染的小鼠骨髓来源的巨噬细胞。我们在已知的结核分枝杆菌应答转录因子和增强子及其靶基因的转录激活之间建立了联系。我们的数据表明，增强子可能通过转录激活关键免疫基因（如Tnf、Tnfrsf 1b、Irg 1、Hilpda、Ccl 3和Ccl 4）来驱动巨噬细胞反应。我们报告增强子获得转录从头感染。最后，我们将高转录诱导增强子与结核分枝杆菌感染中未被认识的基因如Fbxl 3、Tapt 1、Edn 1和Hivep 1的激活联系起来。我们的研究扩展了目前对巨噬细胞对结核分枝杆菌感染的反应的调节的知识，并为将来对该过程中增强子-基因相互作用的功能研究提供了基础。
BackgroundTuberculosis is a life-threatening infectious disease caused by Mycobacterium tuberculosis (M.tb). M.tb subverts host immune responses to build a favourable niche and survive inside of host macrophages. Macrophages can control or eliminate the infection, if acquire appropriate functional phenotypes. Transcriptional regulation is a key process that governs the activation and maintenance of these phenotypes. Among the factors orchestrating transcriptional regulation during M.tb infection, transcriptional enhancers still remain unexplored.ResultsWe analysed transcribed enhancers in M.tb-infected mouse bone marrow-derived macrophages. We established a link between known M.tb-responsive transcription factors and transcriptional activation of enhancers and their target genes. Our data suggest that enhancers might drive macrophage response via transcriptional activation of key immune genes, such as Tnf, Tnfrsf1b, Irg1, Hilpda, Ccl3, and Ccl4. We report enhancers acquiring transcription de novo upon infection. Finally, we link highly transcriptionally induced enhancers to activation of genes with previously unappreciated roles in M.tb infection, such as Fbxl3, Tapt1, Edn1, and Hivep1.ConclusionsOur findings suggest the importance of macrophage host transcriptional enhancers during M.tb infection. Our study extends current knowledge of the regulation of macrophage responses to M.tb infection and provides a basis for future functional studies on enhancer-gene interactions in this process.