Aberrant methylation of host macrophages induced by tuberculosis infection
Aberrant methylation of host macrophages induced by tuberculosis infection
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DOI：
10.1007/s11274-019-2733-7
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发表时间：
2019-11-01
影响因子：
4.1
通讯作者：
Siadat, Seyed Davar
中科院分区：
文献类型：
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作者：
Behrouzi, Ava;Hadifar, Shima;Siadat, Seyed Davar
DNA甲基化已被引入作为不同疾病的有前途的生物标志物。在结核分枝杆菌（Mtb）感染过程中，巨噬细胞DNA甲基化状态的改变已被记录。我们使用人类甲基化PCR阵列试剂盒进行了这项研究，该试剂盒包含TLR 2信号通路中的22个基因，以深入了解药物敏感和耐药Mtb菌株与THP-1衍生的巨噬细胞（TB感染期间的主要宿主免疫细胞之一）之间的表观遗传相互作用。我们还评估了Rv 1988基因在所研究的分离株中的表达。结果发现，与空白对照组相比，广泛耐药（XDR）结核分枝杆菌感染的THP-1巨噬细胞中，除Tbk-2和Tbk-1外，其他所有炎症基因的甲基化水平均升高（P < 0.05）。在敏感菌株中，我们只发现了Ubev，Ube 2n和Traf 6基因的甲基化水平略有增加，除此之外，我们还发现了Ubek-2基因的低甲基化。目前的研究结果提供了新的见解耐药和易感结核分枝杆菌菌株在促进巨噬细胞异常表观遗传修饰的潜在作用。需要对不同结核分枝杆菌感染的宿主表观基因组进行进一步研究，以阐明其在免疫应答中的功能，并引入新的有效的抗结核分枝杆菌感染的工具。
DNA methylation has been introduced as a promising biomarker for different diseases. Alterations in macrophage DNA methylation status have been documented during Mycobacterium tuberculosis (Mtb) infection. We conducted this study using a human methylation PCR array kit, which comprised a panel of 22 genes in TLR2 signaling pathway, in order to gain insights into epigenetic interactions between drug-susceptible and -resistant Mtb strains and THP-1-derived macrophages (one of the main host immunity cells during TB infection). We also evaluated the expression of Rv1988 gene in the studied isolates. It was found that the methylation level of all of the studied inflammatory genes, except Irak-2 and Tbk-1, increased in THP-1 macrophages, which were infected by extensively drug-resistant (XDR) Mtb strains, compared with the mock cells (P < 0.05). In susceptible strains, we only found hypomethylation in Irak-2 gene, in addition to a slight increase in the methylation levels of Ubev, Ube2n, and Traf6 genes. The present findings provide new insights into the potential role of resistant and susceptible Mtb strains in promoting aberrant epigenetic modifications in macrophages. Further investigations on the host epigenomes, infected with different Mtb isolates, are needed to elucidate their functions in immunological responses and to introduce new effective tools against Mtb infection.