Key Macrophage Responses to Infection With Mycobacterium tuberculosis Are Co-Regulated by microRNAs and DNA Methylation.
Key Macrophage Responses to Infection With Mycobacterium tuberculosis Are Co-Regulated by microRNAs and DNA Methylation.
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DOI：
10.3389/fimmu.2021.685237
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发表时间：
2021
影响因子：
7.3
通讯作者：
Karakousis PC
中科院分区：
文献类型：
--
作者：
Looney M;Lorenc R;Halushka MK;Karakousis PC
结核病（TB）是单一细菌病原体感染导致死亡的主要原因。宿主巨噬细胞是感染结核分枝杆菌（Mtb）的主要细胞类型，结核分枝杆菌是引起结核病的生物体。巨噬细胞反应途径受多种因素调节，包括microRNAs （miRNAs）和表观遗传变化，这些因素可以影响感染的结果。尽管在结核分枝杆菌感染的背景下已经研究了mirna和DNA甲基化的失调，但尚未有研究调查这两个过程如何在原代人巨噬细胞中共同调节关键的抗结核途径。在当前的研究中，我们将mtb感染的原代人巨噬细胞的miRNA丰度和DNA甲基化状态的全基因组分析与mRNA转录组学相结合，以破译巨噬细胞的哪些功能可能受到这两种调节的控制。通过体外巨噬细胞感染模型和下一代测序，我们发现mirna和甲基化变化共同调节重要的巨噬细胞反应过程，包括免疫细胞激活、巨噬细胞代谢和AMPK通路信号传导。
Tuberculosis (TB) is the leading cause of death from infection with a single bacterial pathogen. Host macrophages are the primary cell type infected with Mycobacterium tuberculosis (Mtb), the organism that causes TB. Macrophage response pathways are regulated by various factors, including microRNAs (miRNAs) and epigenetic changes that can shape the outcome of infection. Although dysregulation of both miRNAs and DNA methylation have been studied in the context of Mtb infection, studies have not yet investigated how these two processes may jointly co-regulate critical anti-TB pathways in primary human macrophages. In the current study, we integrated genome-wide analyses of miRNA abundance and DNA methylation status with mRNA transcriptomics in Mtb-infected primary human macrophages to decipher which macrophage functions may be subject to control by these two types of regulation. Using in vitro macrophage infection models and next generation sequencing, we found that miRNAs and methylation changes co-regulate important macrophage response processes, including immune cell activation, macrophage metabolism, and AMPK pathway signaling.
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影响因子：
14.9
作者：
Feng H;Conneely KN;Wu H
通讯作者：
Wu H
影响因子：
3.9
作者：
Anastasiadi D;Esteve-Codina A;Piferrer F
通讯作者：
Piferrer F
DOI：
10.1016/j.tube.2013.08.004
发表时间：
2013-11
期刊：
Tuberculosis (Edinburgh, Scotland)
影响因子：
--
作者：
Harapan H;Fitra F;Ichsan I;Mulyadi M;Miotto P;Hasan NA;Calado M;Cirillo DM
通讯作者：
Cirillo DM
影响因子：
14.9
作者：
Chang, Le;Zhou, Guangyan;Xia, Jianguo
通讯作者：
Xia, Jianguo
影响因子：
14.9
作者：
Fromm, Bastian;Domanska, Diana;Peterson, Kevin J.
通讯作者：
Peterson, Kevin J.