MicroRNA-325-3p Facilitates Immune Escape of <named-content content-type="genus-species">Mycobacterium tuberculosis</named-content> through Targeting LNX1 via NEK6 Accumulation to Promote Anti-Apoptotic STAT3 Signaling

ABSTRACT Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis that poses threats to the public. M. tuberculosis survives in macrophages by escaping from immune surveillance and clearance, which exacerbates the bacterial proliferation. However, the molecular mechanisms of t...

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Autores principales:	Beibei Fu, Weiwei Xue, Haiwei Zhang, Rui Zhang, Kelly Feldman, Qingting Zhao, Shanfu Zhang, Lei Shi, Krishna Chaitanya Pavani, Weiqi Nian, Xiaoyuan Lin, Haibo Wu
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	Mycobacterium tuberculosis microRNA macrophage ubiquitination immune escape Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/1fcb31eb482147c2b27ae82d12c46dab
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spelling	oai:doaj.org-article:1fcb31eb482147c2b27ae82d12c46dab2021-11-15T15:56:47ZMicroRNA-325-3p Facilitates Immune Escape of <named-content content-type="genus-species">Mycobacterium tuberculosis</named-content> through Targeting LNX1 via NEK6 Accumulation to Promote Anti-Apoptotic STAT3 Signaling10.1128/mBio.00557-202150-7511https://doaj.org/article/1fcb31eb482147c2b27ae82d12c46dab2020-06-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00557-20https://doaj.org/toc/2150-7511ABSTRACT Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis that poses threats to the public. M. tuberculosis survives in macrophages by escaping from immune surveillance and clearance, which exacerbates the bacterial proliferation. However, the molecular mechanisms of this immune escape have not yet been fully understood. Using multiple cell and mouse models, we found that microRNA-325-3p (miR-325-3p) is upregulated after M. tuberculosis infection and Mir325-deficient mice show resistance to M. tuberculosis. We demonstrated that miR-325-3p directly targets LNX1, an E3 ubiquitin ligase of NEK6, and that this hampers the proteasomal degradation of NEK6 in macrophages. The abnormal accumulation of NEK6 leads to the activation of STAT3 signaling, thus inhibiting the process of apoptosis and promoting the intracellular survival of M. tuberculosis. Our findings not only reveal a new immune escape pathway of M. tuberculosis but also may provide new insights into the development of therapeutic approaches for drug-resistant TB. IMPORTANCE Intracellular survival of Mycobacterium tuberculosis results in bacterial proliferation and the spread of infection in lungs, consequently deteriorating the conditions of tuberculosis (TB) patients. This research discovers a new immune escape pathway of M. tuberculosis by modulating host miR-325-3p expression, thus leading to the intracellular survival of M. tuberculosis. These findings make a contribution to the understanding of the immune escape of M. tuberculosis, and they provide a theoretical basis for the development of therapeutic approaches for drug-resistant TB.Beibei FuWeiwei XueHaiwei ZhangRui ZhangKelly FeldmanQingting ZhaoShanfu ZhangLei ShiKrishna Chaitanya PavaniWeiqi NianXiaoyuan LinHaibo WuAmerican Society for MicrobiologyarticleMycobacterium tuberculosismicroRNAmacrophageubiquitinationimmune escapeMicrobiologyQR1-502ENmBio, Vol 11, Iss 3 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Mycobacterium tuberculosis microRNA macrophage ubiquitination immune escape Microbiology QR1-502
spellingShingle	Mycobacterium tuberculosis microRNA macrophage ubiquitination immune escape Microbiology QR1-502 Beibei Fu Weiwei Xue Haiwei Zhang Rui Zhang Kelly Feldman Qingting Zhao Shanfu Zhang Lei Shi Krishna Chaitanya Pavani Weiqi Nian Xiaoyuan Lin Haibo Wu MicroRNA-325-3p Facilitates Immune Escape of <named-content content-type="genus-species">Mycobacterium tuberculosis</named-content> through Targeting LNX1 via NEK6 Accumulation to Promote Anti-Apoptotic STAT3 Signaling
description	ABSTRACT Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis that poses threats to the public. M. tuberculosis survives in macrophages by escaping from immune surveillance and clearance, which exacerbates the bacterial proliferation. However, the molecular mechanisms of this immune escape have not yet been fully understood. Using multiple cell and mouse models, we found that microRNA-325-3p (miR-325-3p) is upregulated after M. tuberculosis infection and Mir325-deficient mice show resistance to M. tuberculosis. We demonstrated that miR-325-3p directly targets LNX1, an E3 ubiquitin ligase of NEK6, and that this hampers the proteasomal degradation of NEK6 in macrophages. The abnormal accumulation of NEK6 leads to the activation of STAT3 signaling, thus inhibiting the process of apoptosis and promoting the intracellular survival of M. tuberculosis. Our findings not only reveal a new immune escape pathway of M. tuberculosis but also may provide new insights into the development of therapeutic approaches for drug-resistant TB. IMPORTANCE Intracellular survival of Mycobacterium tuberculosis results in bacterial proliferation and the spread of infection in lungs, consequently deteriorating the conditions of tuberculosis (TB) patients. This research discovers a new immune escape pathway of M. tuberculosis by modulating host miR-325-3p expression, thus leading to the intracellular survival of M. tuberculosis. These findings make a contribution to the understanding of the immune escape of M. tuberculosis, and they provide a theoretical basis for the development of therapeutic approaches for drug-resistant TB.
format	article
author	Beibei Fu Weiwei Xue Haiwei Zhang Rui Zhang Kelly Feldman Qingting Zhao Shanfu Zhang Lei Shi Krishna Chaitanya Pavani Weiqi Nian Xiaoyuan Lin Haibo Wu
author_facet	Beibei Fu Weiwei Xue Haiwei Zhang Rui Zhang Kelly Feldman Qingting Zhao Shanfu Zhang Lei Shi Krishna Chaitanya Pavani Weiqi Nian Xiaoyuan Lin Haibo Wu
author_sort	Beibei Fu
title	MicroRNA-325-3p Facilitates Immune Escape of <named-content content-type="genus-species">Mycobacterium tuberculosis</named-content> through Targeting LNX1 via NEK6 Accumulation to Promote Anti-Apoptotic STAT3 Signaling
title_short	MicroRNA-325-3p Facilitates Immune Escape of <named-content content-type="genus-species">Mycobacterium tuberculosis</named-content> through Targeting LNX1 via NEK6 Accumulation to Promote Anti-Apoptotic STAT3 Signaling
title_full	MicroRNA-325-3p Facilitates Immune Escape of <named-content content-type="genus-species">Mycobacterium tuberculosis</named-content> through Targeting LNX1 via NEK6 Accumulation to Promote Anti-Apoptotic STAT3 Signaling
title_fullStr	MicroRNA-325-3p Facilitates Immune Escape of <named-content content-type="genus-species">Mycobacterium tuberculosis</named-content> through Targeting LNX1 via NEK6 Accumulation to Promote Anti-Apoptotic STAT3 Signaling
title_full_unstemmed	MicroRNA-325-3p Facilitates Immune Escape of <named-content content-type="genus-species">Mycobacterium tuberculosis</named-content> through Targeting LNX1 via NEK6 Accumulation to Promote Anti-Apoptotic STAT3 Signaling
title_sort	microrna-325-3p facilitates immune escape of <named-content content-type="genus-species">mycobacterium tuberculosis</named-content> through targeting lnx1 via nek6 accumulation to promote anti-apoptotic stat3 signaling
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/1fcb31eb482147c2b27ae82d12c46dab
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MicroRNA-325-3p Facilitates Immune Escape of <named-content content-type="genus-species">Mycobacterium tuberculosis</named-content> through Targeting LNX1 via NEK6 Accumulation to Promote Anti-Apoptotic STAT3 Signaling

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