Mannala Gopala K, Izar Benjamin, Rupp Oliver, Schultze Tilman, Goesmann Alexander, Chakraborty Trinad, Hain Torsten
Institute of Medical Microbiology, Justus-Liebig University, Giessen, Germany.
Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, United States.
Front Microbiol. 2017 Dec 12;8:2463. doi: 10.3389/fmicb.2017.02463. eCollection 2017.
microRNAs (miRNAs) coordinate several physiological and pathological processes by regulating the fate of mRNAs. Studies conducted indicate a role of microRNAs in the control of host-microbe interactions. However, there is limited understanding of miRNA functions in models of bacterial infections. In this study, we systematically explored changes in miRNA expression levels of larvae (greater-wax moth), a model system that recapitulates the vertebrate innate immunity, following infection with . Using an insect-specific miRNA microarray with more than 2000 probes, we found differential expression of 90 miRNAs (39 upregulated and 51 downregulated) in response to infection with . We validated the expression of a subset of miRNAs which have mammalian homologs of known or predicted function. In contrast, non-pathogenic failed to induce these miRNAs, indicating a virulence-dependent miRNA deregulation. To predict miRNA targets using established algorithms, we generated a publically available transcriptome database. We identified miRNA targets involved in innate immunity, signal transduction and autophagy, including spätzle, MAP kinase, and optineurin, respectively, which exhibited a virulence-specific differential expression. Finally, estimation of minimum free energy of miRNA-mRNA duplexes of validated microRNAs and target transcripts revealed a regulatory network of the host immune response to . In conclusion, this study provides evidence for a role of miRNAs in the regulation of the innate immune response following bacterial infection in a simple, rapid and scalable model that may predict host-microbe interactions in higher vertebrates.
微小RNA(miRNA)通过调控信使核糖核酸(mRNA)的命运来协调多种生理和病理过程。已开展的研究表明微小RNA在宿主与微生物相互作用的控制中发挥作用。然而,对于细菌感染模型中miRNA功能的了解有限。在本研究中,我们系统地探究了大蜡螟幼虫(一种概括脊椎动物先天免疫的模型系统)在感染[病原体名称未给出]后miRNA表达水平的变化。使用一种含有2000多个探针的昆虫特异性miRNA微阵列,我们发现90种miRNA(39种上调和51种下调)在感染[病原体名称未给出]后出现差异表达。我们验证了一部分具有已知或预测功能的哺乳动物同源物的miRNA的表达。相比之下,非致病性[对照名称未给出]未能诱导这些miRNA,表明miRNA失调具有毒力依赖性。为了使用既定算法预测miRNA靶标,我们生成了一个可公开获取的转录组数据库。我们鉴定出参与先天免疫、信号转导和自噬的miRNA靶标,分别包括spätzle、丝裂原活化蛋白激酶(MAP激酶)和视紫质神经元蛋白,它们表现出毒力特异性差异表达。最后,对经过验证的miRNA和靶标转录本的miRNA - mRNA双链体的最小自由能估计揭示了宿主对[病原体名称未给出]免疫反应的调控网络。总之,本研究为miRNA在简单、快速且可扩展的模型中细菌感染后先天免疫反应调控中的作用提供了证据,该模型可能预测高等脊椎动物中的宿主 - 微生物相互作用。