Burkholderia pseudomallei-derived miR-3473 enhances NF-κB via targeting TRAF3 and is associated with different inflammatory responses compared to Burkholderia thailandensis in murine macrophages.
Burkholderia pseudomallei-derived miR-3473 enhances NF-κB via targeting TRAF3 and is associated with different inflammatory responses compared to Burkholderia thailandensis in murine macrophages.
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鼻疽伯克霍尔德杆菌衍生的 miR-3473 通过靶向 TRAF3 增强 NF-κ B，并且与小鼠巨噬细胞中的泰国伯克霍尔德杆菌相比，与不同的炎症反应相关
DOI：
10.1186/s12866-016-0901-6
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发表时间：
2016-11-28
期刊：
影响因子：
4.2
通讯作者：
Mao X
中科院分区：
文献类型：
--
作者：
Fang Y;Chen H;Hu Y;Li Q;Hu Z;Ma T;Mao X
鼻疽伯克霍尔德氏菌（Bp）是类鼻疽（一种热带病）的病原体。泰国伯克霍尔德杆菌 (Bt) 与 Bp 具有高度序列相似性，被认为是一种无毒生物。由于 Bp 和 Bt 之间存在许多相似之处，因此它们在宿主反应发病机制和相关机制方面的差异仍然受到削弱。近年来，microRNA在许多疾病中得到了研究，但很少涉及细菌感染、细菌与宿主相互作用或解释毒力和无毒物种之间的差异。我们发现Bp和Bt在RAW264.7巨噬细胞或TC-1肺细胞中的细胞内复制、传播（通过多核巨细胞形成反映）、TNF-α释放和凋亡方面具有相似的表型，但水平不同。特别是在感染后期（感染后 12 小时后），Bp 显示出更快的细胞内生长、更强的细胞毒性和更高的 TNF-α 释放。经过microRNA阵列分析，我们发现一些microRNA在Bp处理的巨噬细胞中显着表达。 miR-3473 是其中之一，在 Bt 处理的巨噬细胞中被特异性诱导，但没有显着变化。此外，TargetScan表明miR-3473可能靶向TRAF3（TNF受体相关因子3），TRAF3是NF-κB途径的众所周知的负调节因子，可能参与Bp感染细胞中TNF-α的诱导和凋亡。在体内，发现Bp处理的小鼠总肺细胞中miR-3473的表达高于Bt处理的小鼠。 miR-3473抑制剂能够减少小鼠TNF-α的释放，延长Bp感染小鼠的生存期。总之，miR-3473通过miR-3473-TRAF3-TNF-α网络在Bp和Bt的差异致病性中发挥重要作用，并调节Bp治疗后TNF-α的释放、细胞凋亡和动物存活。在这项研究中，我们发现了一种特定的 microRNA 与细菌毒力相关，并深入了解了宿主与细菌相互作用的机制，这表明应该应用潜在的寡核苷酸来对抗细菌感染。
Burkholderia pseudomallei (Bp) is the causative agent of melioidosis, a kind of tropical disease. Burkholderia thailandensis (Bt), with a high sequence similarity to Bp, is thought to be an avirulent organism. Since there are numerous similarities between Bp and Bt, their differences in pathogenesis of host response and related mechanism are still undermined. In recent years, microRNAs have been researched in many diseases, but seldom involved in bacterial infection, bacteria-host interaction or explaining the differences between virulent and avirulent species. We found that Bp and Bt had similar phenotypes in terms of intracellular replication, dissemination (reflected by multinucleated giant cell formation), TNF-α release and apoptosis in RAW264.7 macrophages or TC-1 pulmonary cell but in different level. Especially, at the late infection phases (after 12 h post infection), Bp showed faster intracellular growth, stronger cytotoxicity, and higher TNF-α release. After microRNA array analysis, we found some microRNAs were significantly expressed in macrophages treated by Bp. miR-3473 was one of them specifically induced, but not significantly changed in Bt-treated macrophages. In addition, TargetScan suggested that miR-3473 possibly target TRAF3 (TNF receptor-associated factor 3), a well-known negative regulator of the NF-κB pathway, which was probably involved in the TNF-α induction and apoptosis in cells with Bp infection. In vivo, it was found that miR-3473 expression of total lungs cells from Bp-treated was higher than that from Bt-treated mice. And miR-3473 inhibitor was able to decrease the TNF-α release of mice and prolong the survival of mice with Bp infection. In sum, miR-3473 plays an important role in the differential pathogenicity of Bp and Bt via miR-3473-TRAF3-TNF-α network, and regulates TNF-α release, cell apoptosis and animal survival after Bp treatment. In this study, we have found a specific microRNA is related to bacterial virulence and provide insight into the mechanism for host-bacteria interaction, which suggests that potential oligonucleotides should be applied against bacterial infection.
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影响因子：
4.2
作者：
Ngamdee W;Tandhavanant S;Wikraiphat C;Reamtong O;Wuthiekanun V;Salje J;Low DA;Peacock SJ;Chantratita N
通讯作者：
Chantratita N
DOI：
10.1099/00207713-48-1-317
发表时间：
1998-01-01
期刊：
INTERNATIONAL JOURNAL OF SYSTEMATIC BACTERIOLOGY
影响因子：
--
作者：
Brett, PJ;DeShazer, D;Woods, DE
通讯作者：
Woods, DE
影响因子：
4.2
作者：
Brett, PJ;Deshazer, D;Woods, DE
通讯作者：
Woods, DE
鼻疽伯克霍尔德氏菌在肺上皮细胞中的存活受益于 miRNA 介导的 ATG10 抑制
影响因子：
13.3
作者：
Li, Qian;Fang, Yao;Mao, Xu-hu
通讯作者：
Mao, Xu-hu
影响因子：
4.7
作者：
Ordas, Anita;Hegedus, Zoltan;Meijer, Annemarie H.
通讯作者：
Meijer, Annemarie H.