MicroRNA-27b Modulates Inflammatory Response and Apoptosis during Mycobacterium tuberculosis Infection

被引:71
|
作者
Liang, Shuxin [1 ,2 ]
Song, Zhigang [3 ]
Wu, Yongyan [1 ,2 ]
Gao, Yuanpeng [1 ,2 ]
Gao, Mingqing [1 ,2 ]
Liu, Fayang [1 ,2 ]
Wang, Fengyu [1 ,2 ]
Zhang, Yong [1 ,2 ]
机构
[1] Northwest A&F Univ, Coll Vet Med, Yangling 712100, Shaanxi, Peoples R China
[2] Northwest A&F Univ, Key Lab Anim Biotechnol, Minist Agr, 3 Taicheng Rd, Yangling 712100, Shaanxi, Peoples R China
[3] Fudan Univ, Shanghai Publ Hlth Clin Ctr, Dept Pathogen Diag & Biosafety, Shanghai 201508, Peoples R China
来源
JOURNAL OF IMMUNOLOGY | 2018年 / 200卷 / 10期
基金
中国国家自然科学基金;
关键词
ADAPTIVE IMMUNE-RESPONSE; KAPPA-B PATHWAY; ANTIMICROBIAL RESPONSES; HUMAN MACROPHAGES; DENDRITIC CELLS; PROTEIN; EXPRESSION; RESISTANCE; INHIBITOR; SURVIVAL;
D O I
10.4049/jimmunol.1701448
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Mycobacterium tuberculosis poses a significant global health threat. MicroRNAs play an important role in regulating host anti-mycobacterial defense; however, their role in apoptosis-mediated mycobacterial elimination and inflammatory response remains unclear. In this study, we explored the role of microRNA-27b (miR-27b) in murine macrophage responses to M. tuberculosis infection. We uncovered that the TLR-2/MyD88/NF-kappa B signaling pathway induced the expression of miR-27b and miR-27b suppressed the production of proinflammatory factors and the activity of NF-kappa B, thereby avoiding an excessive inflammation during M. tuberculosis infection. Luciferase reporter assay and Western blotting showed that miR-27b directly targeted Bcl-2-associated athanogene 2 (Bag2) in macrophages. Overexpression of Bag2 reversed miR-27b-mediated inhibition of the production of proinflammatory factors. In addition, miR-27b increased p53-dependent cell apoptosis and the production of reactive oxygen species and decreased the bacterial burden. We also showed that Bag2 interacts with p53 and negatively regulates its activity, thereby controlling cell apoptosis and facilitating bacterial survival. In summary, we revealed a novel role of the miR-27b/Bag2 axis in the regulation of inflammatory response and apoptosis and provide a potential molecular host defense mechanism against mycobacteria.
引用
收藏
页码:3506 / 3518
页数:13
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