MiR-21 Is Remotely Governed by the Commensal Bacteria and Impairs Anti-TB Immunity by Down-Regulating IFN-gamma

Yang, Fang1; Yang, Yi1; Chen, Yiwei1; Li, Guobao2; Zhang, Guoliang3; Chen, Lingming1; Zhang, Zhiyi1; Mai, Qiongdan1; Zeng, Gucheng1

2021-01-21

10.3389/fmicb.2020.512581

Frontiers in Microbiology   影响因子和分区

1664-302X

Tuberculosis (TB), which is a frequent and important infectious disease caused by Mycobacterium tuberculosis, has resulted in an extremely high burden of morbidity and mortality. The importance of intestinal dysbacteriosis in regulating host immunity has been implicated in TB, and accumulating evidence suggests that microRNAs (miRNAs) might act as a key mediator in maintaining intestinal homeostasis through signaling networks. However, the involvement of miRNA in gut microbiota, TB and the host immune system remains unknown. Here we showed that intestinal dysbacteriosis increases the susceptibility to TB and remotely increased the expression of miR-21 in lung. Systemic antagonism of miR-21 enhanced IFN-gamma production and further conferred immune protection against TB. Molecular experiments further indicated that miR-21a-3p could specifically target IFN-gamma mRNA. These findings revealed regulatory pathways implicating intestinal dysbacteriosis induced-susceptibility to TB: intestinal dysbiosis -> lung miRNA -> targeting IFN-gamma -> impaired anti-TB immunity. This study also suggested that deregulated miRNAs by commensal bacteria could become promising targets as TB therapeutics.

commensal bacteria miRNA tuberculosis IFN-γ Mycobacterium tuberculosis

SCI

英语

其他

China Postdoctoral Science Foundation[2017M612811] ; National Science and Technology Major Project[2018ZX10715004-002-012] ; Guangdong Science and Technology Project[2018A05056032] ; NSFC[82072250]

Microbiology

Microbiology

WOS:000614410700001

FRONTIERS MEDIA SA

Web of Science

1.Sun Yat Sen Univ, Zhongshan Sch Med, Dept Microbiol, Key Lab Trop Dis Control,Minist Educ, Guangzhou, Peoples R China
2.Southern Univ Sci & Technol, Shenzhen Peoples Hosp 3, Dept TB, Shenzhen, Peoples R China
3.Southern Univ Sci & Technol, Shenzhen Peoples Hosp 3, Natl Clin Res Ctr TB, Guangdong Key Lab Emerging Infect Dis, Shenzhen, Peoples R China

Yang, Fang,Yang, Yi,Chen, Yiwei,et al. MiR-21 Is Remotely Governed by the Commensal Bacteria and Impairs Anti-TB Immunity by Down-Regulating IFN-gamma[J]. Frontiers in Microbiology,2021,11.

Yang, Fang.,Yang, Yi.,Chen, Yiwei.,Li, Guobao.,Zhang, Guoliang.,...&Zeng, Gucheng.(2021).MiR-21 Is Remotely Governed by the Commensal Bacteria and Impairs Anti-TB Immunity by Down-Regulating IFN-gamma.Frontiers in Microbiology,11.

Yang, Fang,et al."MiR-21 Is Remotely Governed by the Commensal Bacteria and Impairs Anti-TB Immunity by Down-Regulating IFN-gamma".Frontiers in Microbiology 11(2021).