Glucocorticoids Suppress Antimicrobial Autophagy and Nitric Oxide Production and Facilitate Mycobacterial Survival in Macrophages

Abstract Chronic administration of glucocorticoids has been shown to render individuals highly susceptible to mycobacterial infection and lead to reactivation of latent bacilli. However, the effect of glucocorticoids on innate anti-mycobacterial defense, especially in macrophages remains largely unk...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Jinli Wang, Ruining Wang, Hui Wang, Xiaofan Yang, Jiahui Yang, Wenjing Xiong, Qian Wen, Li Ma
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/807b1930d06449d1af657b5cc3dbc33d
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:807b1930d06449d1af657b5cc3dbc33d
record_format	dspace
spelling	oai:doaj.org-article:807b1930d06449d1af657b5cc3dbc33d2021-12-02T16:07:44ZGlucocorticoids Suppress Antimicrobial Autophagy and Nitric Oxide Production and Facilitate Mycobacterial Survival in Macrophages10.1038/s41598-017-01174-92045-2322https://doaj.org/article/807b1930d06449d1af657b5cc3dbc33d2017-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-01174-9https://doaj.org/toc/2045-2322Abstract Chronic administration of glucocorticoids has been shown to render individuals highly susceptible to mycobacterial infection and lead to reactivation of latent bacilli. However, the effect of glucocorticoids on innate anti-mycobacterial defense, especially in macrophages remains largely unknown. Here, we found that glucocorticoids inhibited the innate immune response, antimicrobial nitric oxide production and autophagy in mycobacteria-challenged macrophages. Meanwhile, maturation and acidification of mycobacterial phagosomes were attenuated in RAW264.7 cells after glucocorticoids treatment. Consequently, we observed a glucocorticoid-induced increase in the survival of intracellular mycobacteria in both primary macrophages and cell lines. Glucocorticoids treatment decreased the activation of TBK1 kinase, which promotes the maturation of autophagosomes. Inhibition of TBK1 also decreased the production of nitric oxide. Furthermore, several autophagy-related genes were down-regulated, while activation of the Akt/mTOR signaling pathway was increased after glucocorticoids treatment, which may account for autophagy inhibition during mycobacterial infection. Restoration of autophagy with the agonist rapamycin abolished glucocorticoid-mediated enhancement of mycobacterial survival, suggesting that glucocorticoids blocked anti-mycobacterial defense via autophagy inhibition. Collectively, this study demonstrates that glucocorticoids impair innate antimicrobial autophagy and promote mycobacterial survival in macrophages, which is a novel mechanism for glucocorticoid-mediated immunosuppression. Our findings may provide important clues for tuberculosis prevention.Jinli WangRuining WangHui WangXiaofan YangJiahui YangWenjing XiongQian WenLi MaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jinli Wang Ruining Wang Hui Wang Xiaofan Yang Jiahui Yang Wenjing Xiong Qian Wen Li Ma Glucocorticoids Suppress Antimicrobial Autophagy and Nitric Oxide Production and Facilitate Mycobacterial Survival in Macrophages
description	Abstract Chronic administration of glucocorticoids has been shown to render individuals highly susceptible to mycobacterial infection and lead to reactivation of latent bacilli. However, the effect of glucocorticoids on innate anti-mycobacterial defense, especially in macrophages remains largely unknown. Here, we found that glucocorticoids inhibited the innate immune response, antimicrobial nitric oxide production and autophagy in mycobacteria-challenged macrophages. Meanwhile, maturation and acidification of mycobacterial phagosomes were attenuated in RAW264.7 cells after glucocorticoids treatment. Consequently, we observed a glucocorticoid-induced increase in the survival of intracellular mycobacteria in both primary macrophages and cell lines. Glucocorticoids treatment decreased the activation of TBK1 kinase, which promotes the maturation of autophagosomes. Inhibition of TBK1 also decreased the production of nitric oxide. Furthermore, several autophagy-related genes were down-regulated, while activation of the Akt/mTOR signaling pathway was increased after glucocorticoids treatment, which may account for autophagy inhibition during mycobacterial infection. Restoration of autophagy with the agonist rapamycin abolished glucocorticoid-mediated enhancement of mycobacterial survival, suggesting that glucocorticoids blocked anti-mycobacterial defense via autophagy inhibition. Collectively, this study demonstrates that glucocorticoids impair innate antimicrobial autophagy and promote mycobacterial survival in macrophages, which is a novel mechanism for glucocorticoid-mediated immunosuppression. Our findings may provide important clues for tuberculosis prevention.
format	article
author	Jinli Wang Ruining Wang Hui Wang Xiaofan Yang Jiahui Yang Wenjing Xiong Qian Wen Li Ma
author_facet	Jinli Wang Ruining Wang Hui Wang Xiaofan Yang Jiahui Yang Wenjing Xiong Qian Wen Li Ma
author_sort	Jinli Wang
title	Glucocorticoids Suppress Antimicrobial Autophagy and Nitric Oxide Production and Facilitate Mycobacterial Survival in Macrophages
title_short	Glucocorticoids Suppress Antimicrobial Autophagy and Nitric Oxide Production and Facilitate Mycobacterial Survival in Macrophages
title_full	Glucocorticoids Suppress Antimicrobial Autophagy and Nitric Oxide Production and Facilitate Mycobacterial Survival in Macrophages
title_fullStr	Glucocorticoids Suppress Antimicrobial Autophagy and Nitric Oxide Production and Facilitate Mycobacterial Survival in Macrophages
title_full_unstemmed	Glucocorticoids Suppress Antimicrobial Autophagy and Nitric Oxide Production and Facilitate Mycobacterial Survival in Macrophages
title_sort	glucocorticoids suppress antimicrobial autophagy and nitric oxide production and facilitate mycobacterial survival in macrophages
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/807b1930d06449d1af657b5cc3dbc33d
work_keys_str_mv	AT jinliwang glucocorticoidssuppressantimicrobialautophagyandnitricoxideproductionandfacilitatemycobacterialsurvivalinmacrophages AT ruiningwang glucocorticoidssuppressantimicrobialautophagyandnitricoxideproductionandfacilitatemycobacterialsurvivalinmacrophages AT huiwang glucocorticoidssuppressantimicrobialautophagyandnitricoxideproductionandfacilitatemycobacterialsurvivalinmacrophages AT xiaofanyang glucocorticoidssuppressantimicrobialautophagyandnitricoxideproductionandfacilitatemycobacterialsurvivalinmacrophages AT jiahuiyang glucocorticoidssuppressantimicrobialautophagyandnitricoxideproductionandfacilitatemycobacterialsurvivalinmacrophages AT wenjingxiong glucocorticoidssuppressantimicrobialautophagyandnitricoxideproductionandfacilitatemycobacterialsurvivalinmacrophages AT qianwen glucocorticoidssuppressantimicrobialautophagyandnitricoxideproductionandfacilitatemycobacterialsurvivalinmacrophages AT lima glucocorticoidssuppressantimicrobialautophagyandnitricoxideproductionandfacilitatemycobacterialsurvivalinmacrophages
_version_	1718384726578823168

Glucocorticoids Suppress Antimicrobial Autophagy and Nitric Oxide Production and Facilitate Mycobacterial Survival in Macrophages

Ejemplares similares