MicroRNA-106a Inhibits Autophagy Process and Antimicrobial Responses by Targeting ULK1, ATG7, and ATG16L1 During Mycobacterial Infection
Autophagy is a key element of innate immune response against invading pathogens including Mycobacterium tuberculosis (M. tuberculosis). The emerging roles of microRNAs in regulating host antimicrobial responses against M. tuberculosis have gained widespread attention. However, the process by which m...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2020.610021/full |
| _version_ | 1818326993121312768 |
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| author | Kunmei Liu Kunmei Liu Dantong Hong Fan Zhang Xin Li Meng He Xuebo Han Guolin Zhang Guangxian Xu Guangxian Xu Nicola J. Stonehouse Zhongjia Jiang Weijun An Weijun An Le Guo Le Guo Le Guo |
| author_facet | Kunmei Liu Kunmei Liu Dantong Hong Fan Zhang Xin Li Meng He Xuebo Han Guolin Zhang Guangxian Xu Guangxian Xu Nicola J. Stonehouse Zhongjia Jiang Weijun An Weijun An Le Guo Le Guo Le Guo |
| author_sort | Kunmei Liu |
| collection | DOAJ |
| description | Autophagy is a key element of innate immune response against invading pathogens including Mycobacterium tuberculosis (M. tuberculosis). The emerging roles of microRNAs in regulating host antimicrobial responses against M. tuberculosis have gained widespread attention. However, the process by which miRNAs specifically influence antibacterial autophagy during mycobacterial infection is largely uncharacterized. In this study, we demonstrate a novel role of miR-106a in regulating macrophage autophagy against M. tuberculosis. H37Ra infection leads to downregulation of miR-106a in a time- and dose-dependent manner and concomitant upregulation of its three targets (ULK1, ATG7, and ATG16L1) in THP-1 macrophages. MiR-106a could inhibit autophagy activation and antimicrobial responses to M. tuberculosis by targeting ULK1, ATG7, and ATG16L1. Overexpression of miR-106a dramatically inhibited H37Ra-induced activation of autophagy in human THP-1 macrophages, whereas inhibitors of miR-106a remarkably promoted H37Ra-induced autophagy. The inhibitory effect of miR-106a on autophagy process during mycobacterial infection was also confirmed by Transmission Electron Microscope (TEM) observation. More importantly, forced expression of miR-106a increased mycobacterial survival, while transfection with miR-106a inhibitors attenuated the survival of intracellular mycobacteria. Taken together, these data demonstrated that miR-106a functioned as a negative regulator in autophagy and antimicrobial effects by targeting ULK1, ATG7, and ATG16L1 during M. tuberculosis infection, which may provide a potential target for developing diagnostic reagents or antibacterials against tuberculosis. |
| first_indexed | 2024-12-13T12:09:12Z |
| format | Article |
| id | doaj.art-310fdaa8f0fe4258a6a527499080cfc1 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-13T12:09:12Z |
| publishDate | 2021-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-310fdaa8f0fe4258a6a527499080cfc12022-12-21T23:46:53ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-01-011110.3389/fimmu.2020.610021610021MicroRNA-106a Inhibits Autophagy Process and Antimicrobial Responses by Targeting ULK1, ATG7, and ATG16L1 During Mycobacterial InfectionKunmei Liu0Kunmei Liu1Dantong Hong2Fan Zhang3Xin Li4Meng He5Xuebo Han6Guolin Zhang7Guangxian Xu8Guangxian Xu9Nicola J. Stonehouse10Zhongjia Jiang11Weijun An12Weijun An13Le Guo14Le Guo15Le Guo16Ningxia Key Laboratory of Clinical and Pathogenic Microbiology, General Hospital of Ningxia Medical University, Yinchuan, ChinaNingxia Key Laboratory of Cerebrocranial Diseases, Ningxia Medical University, Yinchuan, ChinaDepartment of Medical Laboratory, School of Clinical Medicine, Ningxia Medical University, Yinchuan, ChinaDepartment of Medical Laboratory, School of Clinical Medicine, Ningxia Medical University, Yinchuan, ChinaDepartment of Medical Laboratory, School of Clinical Medicine, Ningxia Medical University, Yinchuan, ChinaDepartment of Medical Laboratory, School of Clinical Medicine, Ningxia Medical University, Yinchuan, ChinaDepartment of Medical Laboratory, School of Clinical Medicine, Ningxia Medical University, Yinchuan, ChinaSuzhou Institute for Drug Control, Suzhou, ChinaNingxia Key Laboratory of Clinical and Pathogenic Microbiology, General Hospital of Ningxia Medical University, Yinchuan, ChinaDepartment of Medical Laboratory, School of Clinical Medicine, Ningxia Medical University, Yinchuan, ChinaSchool of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, United KingdomDepartment of Medical Laboratory, School of Clinical Medicine, Ningxia Medical University, Yinchuan, ChinaNingxia Key Laboratory of Clinical and Pathogenic Microbiology, General Hospital of Ningxia Medical University, Yinchuan, ChinaDepartment of Orthopaedics, General Hospital of Ningxia Medical University, Yinchuan, ChinaNingxia Key Laboratory of Clinical and Pathogenic Microbiology, General Hospital of Ningxia Medical University, Yinchuan, ChinaNingxia Key Laboratory of Cerebrocranial Diseases, Ningxia Medical University, Yinchuan, ChinaDepartment of Medical Laboratory, School of Clinical Medicine, Ningxia Medical University, Yinchuan, ChinaAutophagy is a key element of innate immune response against invading pathogens including Mycobacterium tuberculosis (M. tuberculosis). The emerging roles of microRNAs in regulating host antimicrobial responses against M. tuberculosis have gained widespread attention. However, the process by which miRNAs specifically influence antibacterial autophagy during mycobacterial infection is largely uncharacterized. In this study, we demonstrate a novel role of miR-106a in regulating macrophage autophagy against M. tuberculosis. H37Ra infection leads to downregulation of miR-106a in a time- and dose-dependent manner and concomitant upregulation of its three targets (ULK1, ATG7, and ATG16L1) in THP-1 macrophages. MiR-106a could inhibit autophagy activation and antimicrobial responses to M. tuberculosis by targeting ULK1, ATG7, and ATG16L1. Overexpression of miR-106a dramatically inhibited H37Ra-induced activation of autophagy in human THP-1 macrophages, whereas inhibitors of miR-106a remarkably promoted H37Ra-induced autophagy. The inhibitory effect of miR-106a on autophagy process during mycobacterial infection was also confirmed by Transmission Electron Microscope (TEM) observation. More importantly, forced expression of miR-106a increased mycobacterial survival, while transfection with miR-106a inhibitors attenuated the survival of intracellular mycobacteria. Taken together, these data demonstrated that miR-106a functioned as a negative regulator in autophagy and antimicrobial effects by targeting ULK1, ATG7, and ATG16L1 during M. tuberculosis infection, which may provide a potential target for developing diagnostic reagents or antibacterials against tuberculosis.https://www.frontiersin.org/articles/10.3389/fimmu.2020.610021/fullMycobacterium tuberculosisautophagymiR-106aULK1ATG7ATG16L1 |
| spellingShingle | Kunmei Liu Kunmei Liu Dantong Hong Fan Zhang Xin Li Meng He Xuebo Han Guolin Zhang Guangxian Xu Guangxian Xu Nicola J. Stonehouse Zhongjia Jiang Weijun An Weijun An Le Guo Le Guo Le Guo MicroRNA-106a Inhibits Autophagy Process and Antimicrobial Responses by Targeting ULK1, ATG7, and ATG16L1 During Mycobacterial Infection Frontiers in Immunology Mycobacterium tuberculosis autophagy miR-106a ULK1 ATG7 ATG16L1 |
| title | MicroRNA-106a Inhibits Autophagy Process and Antimicrobial Responses by Targeting ULK1, ATG7, and ATG16L1 During Mycobacterial Infection |
| title_full | MicroRNA-106a Inhibits Autophagy Process and Antimicrobial Responses by Targeting ULK1, ATG7, and ATG16L1 During Mycobacterial Infection |
| title_fullStr | MicroRNA-106a Inhibits Autophagy Process and Antimicrobial Responses by Targeting ULK1, ATG7, and ATG16L1 During Mycobacterial Infection |
| title_full_unstemmed | MicroRNA-106a Inhibits Autophagy Process and Antimicrobial Responses by Targeting ULK1, ATG7, and ATG16L1 During Mycobacterial Infection |
| title_short | MicroRNA-106a Inhibits Autophagy Process and Antimicrobial Responses by Targeting ULK1, ATG7, and ATG16L1 During Mycobacterial Infection |
| title_sort | microrna 106a inhibits autophagy process and antimicrobial responses by targeting ulk1 atg7 and atg16l1 during mycobacterial infection |
| topic | Mycobacterium tuberculosis autophagy miR-106a ULK1 ATG7 ATG16L1 |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2020.610021/full |
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