MiR-25 blunts autophagy and promotes the survival of Mycobacterium tuberculosis by regulating NPC1
Wenqi Dong,
Gaoyan Wang,
Jiajia Feng,
Pei Li,
Rui Wang,
Hao Lu,
Wenjia Lu,
Chenchen Wang,
Xiangru Wang,
Huanchun Chen,
Yaozu Xiang,
Chen Tan
Affiliations
Wenqi Dong
State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China; Hubei Hongshan Laboratory, Wuhan, Hubei, China
Gaoyan Wang
State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China; Hubei Hongshan Laboratory, Wuhan, Hubei, China
Jiajia Feng
State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China; Hubei Hongshan Laboratory, Wuhan, Hubei, China
Pei Li
Department of Gastrointestinal Surgery, The Second Clinical Medical College of Jinan University, Shenzhen, Guangdong, China
Rui Wang
Department of Experimental Animal Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China
Hao Lu
State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China; Hubei Hongshan Laboratory, Wuhan, Hubei, China
Wenjia Lu
State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China; Hubei Hongshan Laboratory, Wuhan, Hubei, China
Chenchen Wang
State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China; Hubei Hongshan Laboratory, Wuhan, Hubei, China
Xiangru Wang
Hubei Hongshan Laboratory, Wuhan, Hubei, China; Key Laboratory of Preventive Veterinary Medicine in Hubei Province, Wuhan, Hubei, China; Key Laboratory of Development of Veterinary Diagnostic Products, Ministry of Agriculture of the People’s Republic of China, Wuhan, Hubei, China
Huanchun Chen
State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China; Hubei Hongshan Laboratory, Wuhan, Hubei, China; Key Laboratory of Preventive Veterinary Medicine in Hubei Province, Wuhan, Hubei, China; Key Laboratory of Development of Veterinary Diagnostic Products, Ministry of Agriculture of the People’s Republic of China, Wuhan, Hubei, China
Yaozu Xiang
School of Life Sciences and Technology, Tongji University, Shanghai, China
Chen Tan
State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China; Hubei Hongshan Laboratory, Wuhan, Hubei, China; Key Laboratory of Preventive Veterinary Medicine in Hubei Province, Wuhan, Hubei, China; Key Laboratory of Development of Veterinary Diagnostic Products, Ministry of Agriculture of the People’s Republic of China, Wuhan, Hubei, China; Corresponding author
Summary: Mycobacterium tuberculosis (Mtb) evades host clearance by inhibiting autophagy. MicroRNA-25 (miR-25) expression was significantly up-regulated in the lung tissues of mice infected with Bacillus Calmette-Guerin (BCG) and macrophages infected with Mtb or BCG, especially in the early stages of infection. MiR-25 can significantly increase the survival of Mtb and BCG in macrophages. We validated that miR-25 targets the NPC1 protein located on the lysosomal membrane, resulting in damage to lysosomal function, thereby inhibiting autophagolysosome formation and promoting the survival of Mtb and BCG. Consistently, mice lacking miR-25 exhibited more resistant to BCG infection. In addition, we found that Rv1759c induces the expression of miR-25 through NFKB inhibitor zeta (NFKBIZ). This study demonstrates that the role of miR-25 during Mtb infection contributes to a better understanding of the pathogenesis of tuberculosis (TB).
