Analysis of miRNA expression profiling in human macrophages responding to Mycobacterium infection: Induction of the immune regulator miR-146a

• Published in: The Journal of infection 2014-06, Vol.68 (6), p.553-561
• Main Authors: Liu, Zhen, Zhou, Guoyong, Deng, Xiangdong, Yu, Qi, Hu, Yongliang, Sun, Huijie, Wang, Zhongyuan, Chen, Hongbing, Jia, Chiyu, Wang, Di
• Format: Article
• Language: English
• Subjects: Bacterial diseases; Biological and medical sciences; Cells, Cultured; Cyclooxygenase 2 - biosynthesis; Gene Expression Profiling; General aspects; Host-Pathogen Interactions; Human bacterial diseases; Humans; Infectious Disease; Infectious diseases; Inflammation; Macrophages - immunology; Macrophages - microbiology; Medical sciences; MicroRNAs - biosynthesis; miR-146a; Mycobacterium bovis; Mycobacterium bovis - immunology; Mycobacterium bovis - isolation & purification; Mycobacterium bovis BCG; Mycobacterium tuberculosis; PTGS2; TNF-α; Tuberculosis and atypical mycobacterial infections; Tuberculosis, Pulmonary - immunology; Tuberculosis, Pulmonary - microbiology; Tumor Necrosis Factor-alpha - biosynthesis
• ISSN: 0163-4453; 1532-2742
• DOI: 10.1016/j.jinf.2013.12.017

Summary Objectives The regulatory mechanism of microRNA (miRNA) within macrophage innative response to Mycobacterium tuberculosis infection is not clear yet. Methods The expression profile of cellular miRNAs during Mycobacterium bovis BCG infection was analyzed by using microarray. The expression of miR-146a was evaluated in alveolar macrophages (AMs) of bronchoalveolar lavage solution from pulmonary tuberculosis (PTB) patients and healthy volunteers respectively. Inhibitor experiment and promoter analysis were used to investigate the pathway involved in the induction of miR-146a. Examination of miR-146a function in macrophages was performed by overexpression and inhibition of miR-146a. Results Among the altered miRNAs, 10 were downregulated whereas 8 were upregulated in M. bovis BCG-infected macrophage. MiR-146a was high expressed in cultured macrophage respond to M. bovis BCG but decreased in AMs of PTB patients, and stated a negative correlation with degree of smear-positive. Nuclear factor-κB pathway was required for the induction of miR-146a. Overexpression of miR-146a results in significant reduction of PTGS2 and enhanced the killing ability of THP-1 cells to intracellular M. bovis BCG, and miR-146a negatively regulated TNF-α release in feedback manner. Conclusions Our findings suggest an important role of miR-146a in M. bovis BCG infection that helps to fine-tune the inflammation response of MTB infection.