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Macrophage-mediated inflammatory response decreases mycobacterial survival in mouse MSCs by augmenting NO production
Mycobacterium tuberculosis (MTB) is a hard-to-eradicate intracellular microbe, which escapes host immune attack during latent infection. Recent studies reveal that mesenchymal stem cells (MSCs) provide a protective niche for MTB to maintain latency. However, the regulation of mycobacterial residency...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4890015/ https://www.ncbi.nlm.nih.gov/pubmed/27251437 http://dx.doi.org/10.1038/srep27326 |
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author | Yang, Kun Wu, Yongjian Xie, Heping Li, Miao Ming, Siqi Li, Liyan Li, Meiyu Wu, Minhao Gong, Sitang Huang, Xi |
author_facet | Yang, Kun Wu, Yongjian Xie, Heping Li, Miao Ming, Siqi Li, Liyan Li, Meiyu Wu, Minhao Gong, Sitang Huang, Xi |
author_sort | Yang, Kun |
collection | PubMed |
description | Mycobacterium tuberculosis (MTB) is a hard-to-eradicate intracellular microbe, which escapes host immune attack during latent infection. Recent studies reveal that mesenchymal stem cells (MSCs) provide a protective niche for MTB to maintain latency. However, the regulation of mycobacterial residency in MSCs in the infectious microenvironment remains largely unknown. Here, we found that macrophage-mediated inflammatory response during MTB infection facilitated the clearance of bacilli residing in mouse MSCs. Higher inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production were observed in mouse MSCs under macrophage-mediated inflammatory circumstance. Blocking NO production in MSCs increased the survival of intracellular mycobacteria, indicating NO-mediated antimycobacterial activity. Moreover, both nuclear factor κB (NF-κB) and Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathways were involved in iNOS expression and NO production in inflammatory microenvironment. Furthermore, pro-inflammatory cytokine interleukin-1β could trigger NO production in MSCs and exert anti-mycobacterial activity via NF-κB signaling pathway. Neutralization of interleukin-1β in macrophage-mediated inflammatory microenvironment dampened the ability of mouse MSCs to produce NO. Together, our findings demonstrated that macrophage-mediated inflammatory response during mycobacterial infection promotes the clearance of bacilli in mouse MSCs by increasing NO production, which may provide a better understanding of latent MTB infection. |
format | Online Article Text |
id | pubmed-4890015 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-48900152016-06-09 Macrophage-mediated inflammatory response decreases mycobacterial survival in mouse MSCs by augmenting NO production Yang, Kun Wu, Yongjian Xie, Heping Li, Miao Ming, Siqi Li, Liyan Li, Meiyu Wu, Minhao Gong, Sitang Huang, Xi Sci Rep Article Mycobacterium tuberculosis (MTB) is a hard-to-eradicate intracellular microbe, which escapes host immune attack during latent infection. Recent studies reveal that mesenchymal stem cells (MSCs) provide a protective niche for MTB to maintain latency. However, the regulation of mycobacterial residency in MSCs in the infectious microenvironment remains largely unknown. Here, we found that macrophage-mediated inflammatory response during MTB infection facilitated the clearance of bacilli residing in mouse MSCs. Higher inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production were observed in mouse MSCs under macrophage-mediated inflammatory circumstance. Blocking NO production in MSCs increased the survival of intracellular mycobacteria, indicating NO-mediated antimycobacterial activity. Moreover, both nuclear factor κB (NF-κB) and Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathways were involved in iNOS expression and NO production in inflammatory microenvironment. Furthermore, pro-inflammatory cytokine interleukin-1β could trigger NO production in MSCs and exert anti-mycobacterial activity via NF-κB signaling pathway. Neutralization of interleukin-1β in macrophage-mediated inflammatory microenvironment dampened the ability of mouse MSCs to produce NO. Together, our findings demonstrated that macrophage-mediated inflammatory response during mycobacterial infection promotes the clearance of bacilli in mouse MSCs by increasing NO production, which may provide a better understanding of latent MTB infection. Nature Publishing Group 2016-06-02 /pmc/articles/PMC4890015/ /pubmed/27251437 http://dx.doi.org/10.1038/srep27326 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Yang, Kun Wu, Yongjian Xie, Heping Li, Miao Ming, Siqi Li, Liyan Li, Meiyu Wu, Minhao Gong, Sitang Huang, Xi Macrophage-mediated inflammatory response decreases mycobacterial survival in mouse MSCs by augmenting NO production |
title | Macrophage-mediated inflammatory response decreases mycobacterial survival in mouse MSCs by augmenting NO production |
title_full | Macrophage-mediated inflammatory response decreases mycobacterial survival in mouse MSCs by augmenting NO production |
title_fullStr | Macrophage-mediated inflammatory response decreases mycobacterial survival in mouse MSCs by augmenting NO production |
title_full_unstemmed | Macrophage-mediated inflammatory response decreases mycobacterial survival in mouse MSCs by augmenting NO production |
title_short | Macrophage-mediated inflammatory response decreases mycobacterial survival in mouse MSCs by augmenting NO production |
title_sort | macrophage-mediated inflammatory response decreases mycobacterial survival in mouse mscs by augmenting no production |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4890015/ https://www.ncbi.nlm.nih.gov/pubmed/27251437 http://dx.doi.org/10.1038/srep27326 |
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