Sirtuin 7 Regulates Nitric Oxide Production and Apoptosis to Promote Mycobacterial Clearance in Macrophages

The host immune system plays a pivotal role in the containment of Mycobacterium tuberculosis (Mtb) infection, and host-directed therapy (HDT) is emerging as an effective strategy to treat tuberculosis (TB), especially drug-resistant TB. Previous studies revealed that expression of sirtuin 7 (SIRT7),...

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Autores principales:	Su Zhang, Yaya Liu, Xuefeng Zhou, Min Ou, Guohui Xiao, Fang Li, Zhongyuan Wang, Zhaoqin Wang, Lei Liu, Guoliang Zhang
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	Mycobacterium tuberculosis SIRT7 nitric oxide apoptosis macrophages Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/fd249f0fbb504cbeb8b815d439d1b8a4
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spelling	oai:doaj.org-article:fd249f0fbb504cbeb8b815d439d1b8a42021-12-03T05:30:24ZSirtuin 7 Regulates Nitric Oxide Production and Apoptosis to Promote Mycobacterial Clearance in Macrophages1664-322410.3389/fimmu.2021.779235https://doaj.org/article/fd249f0fbb504cbeb8b815d439d1b8a42021-12-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.779235/fullhttps://doaj.org/toc/1664-3224The host immune system plays a pivotal role in the containment of Mycobacterium tuberculosis (Mtb) infection, and host-directed therapy (HDT) is emerging as an effective strategy to treat tuberculosis (TB), especially drug-resistant TB. Previous studies revealed that expression of sirtuin 7 (SIRT7), a nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase, was downregulated in macrophages after Mycobacterial infection. Inhibition of SIRT7 with the pan-sirtuin family inhibitor nicotinamide (NAM), or by silencing SIRT7 expression, promoted intracellular growth of Mtb and restricted the generation of nitric oxide (NO). Addition of the exogenous NO donor SNAP abrogated the increased bacterial burden in NAM-treated or SIRT7-silenced macrophages. Furthermore, SIRT7-silenced macrophages displayed a lower frequency of early apoptotic cells after Mycobacterial infection, and this could be reversed by providing exogenous NO. Overall, this study clarified a SIRT7-mediated protective mechanism against Mycobacterial infection through regulation of NO production and apoptosis. SIRT7 therefore has potential to be exploited as a novel effective target for HDT of TB.Su ZhangYaya LiuXuefeng ZhouMin OuGuohui XiaoFang LiZhongyuan WangZhaoqin WangLei LiuGuoliang ZhangFrontiers Media S.A.articleMycobacterium tuberculosisSIRT7nitric oxideapoptosismacrophagesImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Mycobacterium tuberculosis SIRT7 nitric oxide apoptosis macrophages Immunologic diseases. Allergy RC581-607
spellingShingle	Mycobacterium tuberculosis SIRT7 nitric oxide apoptosis macrophages Immunologic diseases. Allergy RC581-607 Su Zhang Yaya Liu Xuefeng Zhou Min Ou Guohui Xiao Fang Li Zhongyuan Wang Zhaoqin Wang Lei Liu Guoliang Zhang Sirtuin 7 Regulates Nitric Oxide Production and Apoptosis to Promote Mycobacterial Clearance in Macrophages
description	The host immune system plays a pivotal role in the containment of Mycobacterium tuberculosis (Mtb) infection, and host-directed therapy (HDT) is emerging as an effective strategy to treat tuberculosis (TB), especially drug-resistant TB. Previous studies revealed that expression of sirtuin 7 (SIRT7), a nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase, was downregulated in macrophages after Mycobacterial infection. Inhibition of SIRT7 with the pan-sirtuin family inhibitor nicotinamide (NAM), or by silencing SIRT7 expression, promoted intracellular growth of Mtb and restricted the generation of nitric oxide (NO). Addition of the exogenous NO donor SNAP abrogated the increased bacterial burden in NAM-treated or SIRT7-silenced macrophages. Furthermore, SIRT7-silenced macrophages displayed a lower frequency of early apoptotic cells after Mycobacterial infection, and this could be reversed by providing exogenous NO. Overall, this study clarified a SIRT7-mediated protective mechanism against Mycobacterial infection through regulation of NO production and apoptosis. SIRT7 therefore has potential to be exploited as a novel effective target for HDT of TB.
format	article
author	Su Zhang Yaya Liu Xuefeng Zhou Min Ou Guohui Xiao Fang Li Zhongyuan Wang Zhaoqin Wang Lei Liu Guoliang Zhang
author_facet	Su Zhang Yaya Liu Xuefeng Zhou Min Ou Guohui Xiao Fang Li Zhongyuan Wang Zhaoqin Wang Lei Liu Guoliang Zhang
author_sort	Su Zhang
title	Sirtuin 7 Regulates Nitric Oxide Production and Apoptosis to Promote Mycobacterial Clearance in Macrophages
title_short	Sirtuin 7 Regulates Nitric Oxide Production and Apoptosis to Promote Mycobacterial Clearance in Macrophages
title_full	Sirtuin 7 Regulates Nitric Oxide Production and Apoptosis to Promote Mycobacterial Clearance in Macrophages
title_fullStr	Sirtuin 7 Regulates Nitric Oxide Production and Apoptosis to Promote Mycobacterial Clearance in Macrophages
title_full_unstemmed	Sirtuin 7 Regulates Nitric Oxide Production and Apoptosis to Promote Mycobacterial Clearance in Macrophages
title_sort	sirtuin 7 regulates nitric oxide production and apoptosis to promote mycobacterial clearance in macrophages
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/fd249f0fbb504cbeb8b815d439d1b8a4
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Sirtuin 7 Regulates Nitric Oxide Production and Apoptosis to Promote Mycobacterial Clearance in Macrophages

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