Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Liu, Kunmei, Hong, Dantong, Zhang, Fan, Li, Xin, He, Meng, Han, Xuebo, Zhang, Guolin, Xu, Guangxian, Stonehouse, Nicola J., Jiang, Zhongjia, An, Weijun, Guo, Le
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7832394/
https://www.ncbi.nlm.nih.gov/pubmed/33505399
http://dx.doi.org/10.3389/fimmu.2020.610021
_version_ 1783641827077783552
author Liu, Kunmei
Hong, Dantong
Zhang, Fan
Li, Xin
He, Meng
Han, Xuebo
Zhang, Guolin
Xu, Guangxian
Stonehouse, Nicola J.
Jiang, Zhongjia
An, Weijun
Guo, Le
author_facet Liu, Kunmei
Hong, Dantong
Zhang, Fan
Li, Xin
He, Meng
Han, Xuebo
Zhang, Guolin
Xu, Guangxian
Stonehouse, Nicola J.
Jiang, Zhongjia
An, Weijun
Guo, Le
author_sort Liu, Kunmei
collection PubMed
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.
format Online
Article
Text
id pubmed-7832394
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-78323942021-01-26 MicroRNA-106a Inhibits Autophagy Process and Antimicrobial Responses by Targeting ULK1, ATG7, and ATG16L1 During Mycobacterial Infection Liu, Kunmei Hong, Dantong Zhang, Fan Li, Xin He, Meng Han, Xuebo Zhang, Guolin Xu, Guangxian Stonehouse, Nicola J. Jiang, Zhongjia An, Weijun Guo, Le Front Immunol Immunology 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. Frontiers Media S.A. 2021-01-05 /pmc/articles/PMC7832394/ /pubmed/33505399 http://dx.doi.org/10.3389/fimmu.2020.610021 Text en Copyright © 2020 Liu, Hong, Zhang, Li, He, Han, Zhang, Xu, Stonehouse, Jiang, An and Guo http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Liu, Kunmei
Hong, Dantong
Zhang, Fan
Li, Xin
He, Meng
Han, Xuebo
Zhang, Guolin
Xu, Guangxian
Stonehouse, Nicola J.
Jiang, Zhongjia
An, Weijun
Guo, Le
MicroRNA-106a Inhibits Autophagy Process and Antimicrobial Responses by Targeting ULK1, ATG7, and ATG16L1 During Mycobacterial Infection
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 Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7832394/
https://www.ncbi.nlm.nih.gov/pubmed/33505399
http://dx.doi.org/10.3389/fimmu.2020.610021
work_keys_str_mv AT liukunmei microrna106ainhibitsautophagyprocessandantimicrobialresponsesbytargetingulk1atg7andatg16l1duringmycobacterialinfection
AT hongdantong microrna106ainhibitsautophagyprocessandantimicrobialresponsesbytargetingulk1atg7andatg16l1duringmycobacterialinfection
AT zhangfan microrna106ainhibitsautophagyprocessandantimicrobialresponsesbytargetingulk1atg7andatg16l1duringmycobacterialinfection
AT lixin microrna106ainhibitsautophagyprocessandantimicrobialresponsesbytargetingulk1atg7andatg16l1duringmycobacterialinfection
AT hemeng microrna106ainhibitsautophagyprocessandantimicrobialresponsesbytargetingulk1atg7andatg16l1duringmycobacterialinfection
AT hanxuebo microrna106ainhibitsautophagyprocessandantimicrobialresponsesbytargetingulk1atg7andatg16l1duringmycobacterialinfection
AT zhangguolin microrna106ainhibitsautophagyprocessandantimicrobialresponsesbytargetingulk1atg7andatg16l1duringmycobacterialinfection
AT xuguangxian microrna106ainhibitsautophagyprocessandantimicrobialresponsesbytargetingulk1atg7andatg16l1duringmycobacterialinfection
AT stonehousenicolaj microrna106ainhibitsautophagyprocessandantimicrobialresponsesbytargetingulk1atg7andatg16l1duringmycobacterialinfection
AT jiangzhongjia microrna106ainhibitsautophagyprocessandantimicrobialresponsesbytargetingulk1atg7andatg16l1duringmycobacterialinfection
AT anweijun microrna106ainhibitsautophagyprocessandantimicrobialresponsesbytargetingulk1atg7andatg16l1duringmycobacterialinfection
AT guole microrna106ainhibitsautophagyprocessandantimicrobialresponsesbytargetingulk1atg7andatg16l1duringmycobacterialinfection