Perturbed microRNA Expression by Mycobacterium tuberculosis Promotes Macrophage Polarization Leading to Pro-survival Foam Cell.
Perturbed microRNA Expression by Mycobacterium tuberculosis Promotes Macrophage Polarization Leading to Pro-survival Foam Cell.
复制标题
DOI：
10.3389/fimmu.2017.00107
复制
发表时间：
2017
影响因子：
7.3
通讯作者：
Prajapati VK
中科院分区：
文献类型：
--
作者：
Ahluwalia PK;Pandey RK;Sehajpal PK;Prajapati VK
结核病（TB）是世界范围内的主要死因之一，其中95%的死亡发生在发展中国家，如印度。结核分枝杆菌（Mycobacterium tuberculosis，MTb）是一种具有强大免疫防御能力的病原菌。巨噬细胞是一种吞噬细胞，对抗MTb的免疫至关重要。这些是依赖于环境的高度可塑性细胞，可以显示M1/M2极化。M1巨噬细胞具有杀菌作用，但M2巨噬细胞在其免疫反应中具有抗炎作用。这项计算研究是为了阐明影响MTb在巨噬细胞中存活的miRNA的作用。为了识别针对关键转录因子的miRNA，我们仅从TargetScan数据库中选择保守的命中。此外，使用四个数据库即DIANA-microT、miRDB、miRanda-mirSVR和miRNAMap实现这些miRNA的验证。所有miRNAs均通过转录因子3′-UTR的保守种子序列进行鉴定。生物信息学研究发现，miR-27 a和miR-27 b在IRF 4的3′-UTR处有一个推定的结合位点，miR-302 c在IRF 5处有一个推定的结合位点。miR-155、miR-132和miR-455- 5 p是预测的针对细胞因子信号传导转录因子抑制因子的microRNA。本研究还预测了其他几种对关键转录因子具有亲和力的microRNA。这种MTb相关的microRNA调节以修饰靶基因的表达在TB发病机制中起关键作用。除了M1/M2可塑性之外，MTb还具有将巨噬细胞转化为富含脂质和胆固醇的泡沫细胞的能力。我们强调了M2/泡沫细胞连续体之间重叠的一些microRNA。miR-155、miR-33、miR-27 a和miR-27 b在决定巨噬细胞极性及其向泡沫细胞的转化中起双重作用。这项研究显示了微RNA的一瞥，这些微RNA可以被MTb调节，不仅可以阻止其消除，还可以促进其存活。
Tuberculosis (TB) is one of the prevalent causes of death worldwide, with 95% of these deaths occurring in developing countries, like India. The causative agent, Mycobacterium tuberculosis (MTb) has the tenacious ability to circumvent the host’s immune system for its own advantage. Macrophages are one of the phagocytic cells that are central to immunity against MTb. These are highly plastic cells dependent on the milieu and can showcase M1/M2 polarization. M1 macrophages are bactericidal in action, but M2 macrophages are anti-inflammatory in their immune response. This computational study is an effort to elucidate the role of miRNAs that influences the survival of MTb in the macrophage. To identify the miRNAs against critical transcription factors, we selected only conserved hits from TargetScan database. Further, validation of these miRNAs was achieved using four databases viz. DIANA-microT, miRDB, miRanda-mirSVR, and miRNAMap. All miRNAs were identified through a conserved seed sequence against the 3′-UTR of transcription factors. This bioinformatics study found that miR-27a and miR-27b has a putative binding site at 3′-UTR of IRF4, and miR-302c against IRF5. miR-155, miR-132, and miR-455-5p are predicted microRNAs against suppressor of cytokine signaling transcription factors. Several other microRNAs, which have an affinity for critical transcription factors, are also predicted in this study. This MTb-associated modulation of microRNAs to modify the expression of the target gene(s) plays a critical role in TB pathogenesis. Other than M1/M2 plasticity, MTb has the ability to convert macrophage into foam cells that are rich in lipids and cholesterol. We have highlighted few microRNAs which overlap between M2/foam cell continuums. miR-155, miR-33, miR-27a, and miR-27b plays a dual role in deciding macrophage polarity and its conversion to foam cells. This study shows a glimpse of microRNAs which can be modulated by MTb not only to prevent its elimination but also to promote its survival.