MicroRNA-223 Is Upregulated in Active Tuberculosis Patients and Inhibits Apoptosis of Macrophages by Targeting FOXO3.
BACKGROUND
Macrophage apoptosis is a host innate defense mechanism against tuberculosis (TB).


OBJECTIVE
In this study, we aimed to investigate the role of microRNA-223 (miR-223) in macrophage apoptosis of TB.


METHODS
We analyzed apoptosis in peripheral blood macrophages of active TB patients, infected human macrophages (TDMs and MDMs) with the Mycobacterium tuberculosis (Mtb) strain H37Rv, and observed the expression of miR-223 to investigate the relationship between miR-223 and macrophage apoptosis induced by Mtb.


RESULTS
The apoptosis rate of peripheral blood macrophages decreased in active TB patients compared with healthy controls, and miR-223 expression increased significantly in macrophages after H37Rv infection. Transfection of human macrophages (TDMs and MDMs) with miR-223 inhibited macrophage apoptosis. We also demonstrated that miR-223 directly suppressed forkhead box O3 (FOXO3), and FOXO3 played a critical role as a mediator of the biological effects of miR-223 in macrophage apoptosis. The overexpression of FOXO3 remarkably reversed the apoptosis inhibitory effect of miR-223.


CONCLUSIONS
Our data provide new clues for the essential role of miR-223 in the regulation of anti-Mtb-directed immune responses, which relies on the regulation of FOXO3 expression.
Department of Tuberculosis, The First Hospital Affiliated to the Xinxiang Medical College , Xinxiang, Henan, China .
Xiue
X
Xi
Department of Tuberculosis, The First Hospital Affiliated to the Xinxiang Medical College , Xinxiang, Henan, China .
Chunxiao
C
Zhang
Department of Tuberculosis, The First Hospital Affiliated to the Xinxiang Medical College , Xinxiang, Henan, China .
Wei
W
Han
Department of Tuberculosis, The First Hospital Affiliated to the Xinxiang Medical College , Xinxiang, Henan, China .
Huayang
H
Zhao
Department of Tuberculosis, The First Hospital Affiliated to the Xinxiang Medical College , Xinxiang, Henan, China .
Huiqiang
H
Zhang
Department of Tuberculosis, The First Hospital Affiliated to the Xinxiang Medical College , Xinxiang, Henan, China .
Junhua
J
Jiao
D000328:Adult; D017209:Apoptosis; D005260:Female; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000096:biosynthesis* / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D008264:Macrophages / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis* / Q000276:immunology; D008875:Middle Aged; D014397:Tuberculosis, Pulmonary / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation
D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; D035683:MicroRNAs; C499517:FOXO3 protein, human; C525067:MIR223, human