MicroRNA-155 Modulates Macrophages' Response to Non-Tuberculous Mycobacteria through COX-2/PGE2 Signaling.
MicroRNA-155 Modulates Macrophages' Response to Non-Tuberculous Mycobacteria through COX-2/PGE2 Signaling.
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DOI：
10.3390/pathogens10080920
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发表时间：
2021-07-21
期刊：
影响因子：
--
通讯作者：
Sadikot RT
中科院分区：
文献类型：
--
作者：
Yuan Z;Prasla Z;Lee FE;Bedi B;Sutliff RL;Sadikot RT
非结核分枝杆菌 (NTM) 已被认为是多种人类疾病的病原体，包括免疫功能低下患者（例如艾滋病毒感染者）的严重感染。最常见的菌种是鸟分枝杆菌-胞内复合体 (MAI/MAC)，占大多数感染。尽管有大量信息详细说明了 NTM 的临床意义，但人们对 NTM 感染中宿主与病原体的相互作用知之甚少。 MicroRNA (miR) 是基因表达的重要转录后调节因子。使用微阵列图谱，我们发现感染 NTM 的小鼠骨髓源性巨噬细胞和健康志愿者源性单核细胞巨噬细胞中 miR-155 和环加氧酶 2 (COX-2) 的表达显着增加。针对 miR-155 的 Antagomir 有效抑制 COX-2 的表达并减少前列腺素 E2（PGE2）的分泌，表明 COX-2/PGE2 的表达依赖于 miR-155。从机制上讲，我们发现抑制 NF-κB 活性可显着降低受感染巨噬细胞中 miR-155/COX-2 的表达。最重要的是，阻断 COX-2、E-前列腺素受体（EP2 和 EP4）可增强巨噬细胞中 MAI 的杀伤作用。这些发现为 miR-155/COX-2/PGE2 信号传导的作用提供了新的机制见解，并表明这些途径的诱导可增强巨噬细胞中分枝杆菌的存活。定义宿主与病原体的相互作用可以为难以治疗的 NTM 感染带来新的免疫调节疗法。
Non-tuberculous mycobacteria (NTM) have been recognized as a causative agent of various human diseases, including severe infections in immunocompromised patients, such as people living with HIV. The most common species identified is the Mycobacterium avium-intracellulare complex (MAI/MAC), accounting for a majority of infections. Despite abundant information detailing the clinical significance of NTM, little is known about host–pathogen interactions in NTM infection. MicroRNAs (miRs) serve as important post-transcriptional regulators of gene expression. Using a microarray profile, we found that the expression of miR-155 and cyclo-oxygenase 2 (COX-2) is significantly increased in bone-marrow-derived macrophages from mice and human monocyte-derived macrophages from healthy volunteers that are infected with NTM. Antagomir against miR-155 effectively suppressed expression of COX-2 and reduced Prostaglandin E2(PGE2) secretion, suggesting that COX-2/PGE2 expression is dependent on miR-155. Mechanistically, we found that inhibition of NF-κB activity significantly reduced miR-155/COX-2 expression in infected macrophages. Most importantly, blockade of COX-2, E-prostanoid receptors (EP2 and EP4) enhanced killing of MAI in macrophages. These findings provide novel mechanistic insights into the role of miR-155/COX-2/PGE2 signalling and suggest that induction of these pathways enhances survival of mycobacteria in macrophages. Defining host–pathogen interactions can lead to novel immunomodulatory therapies for NTM infections which are difficult to treat.
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DOI：
10.1084/jem.20080767
发表时间：
2008-11-24
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Chen M;Divangahi M;Gan H;Shin DS;Hong S;Lee DM;Serhan CN;Behar SM;Remold HG
通讯作者：
Remold HG
DOI：
10.1164/rccm.201807-1273pp
发表时间：
2019-04-15
影响因子：
24.7
作者：
Daniel-Wayman, Shelby;Abate, Getahun;Zelazny, Adrian M.
通讯作者：
Zelazny, Adrian M.
影响因子：
4.4
作者：
Aronoff, David M.;Lewis, Casey;Mancuso, Peter
通讯作者：
Mancuso, Peter
影响因子：
15.9
作者：
Dorhoi, Anca;Iannaccone, Marco;Kaufmann, Stefan H. E.
通讯作者：
Kaufmann, Stefan H. E.
影响因子：
3.8
作者：
Comer, Brian S.
通讯作者：
Comer, Brian S.