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Different Signaling Pathways Define Different Interferon-Stimulated Gene Expression during Mycobacteria Infection in Macrophages

Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) represents one of the greatest threats to human health., Interferons (IFNs) in combination with the first-line of anti-TB drugs have been used for treating TB for decades in the clinic, but how Mtb infection regulates interferon-stimulated...

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Autores principales: Zhou, Xinying, Yang, Jiahui, Zhang, Zelin, Zhang, Lijie, Zhu, Bo, Lie, Linmiao, Huang, Yubin, Ma, Rui, Zhou, Chaoying, Hu, Shengfeng, Wen, Qian, Ma, Li
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6387094/
https://www.ncbi.nlm.nih.gov/pubmed/30717477
http://dx.doi.org/10.3390/ijms20030663
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author Zhou, Xinying
Yang, Jiahui
Zhang, Zelin
Zhang, Lijie
Zhu, Bo
Lie, Linmiao
Huang, Yubin
Ma, Rui
Zhou, Chaoying
Hu, Shengfeng
Wen, Qian
Ma, Li
author_facet Zhou, Xinying
Yang, Jiahui
Zhang, Zelin
Zhang, Lijie
Zhu, Bo
Lie, Linmiao
Huang, Yubin
Ma, Rui
Zhou, Chaoying
Hu, Shengfeng
Wen, Qian
Ma, Li
author_sort Zhou, Xinying
collection PubMed
description Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) represents one of the greatest threats to human health., Interferons (IFNs) in combination with the first-line of anti-TB drugs have been used for treating TB for decades in the clinic, but how Mtb infection regulates interferon-stimulated genes (ISGs) in human macrophages (Mϕs) remains unknown. In this study, we investigated the expression-signature and associated innate signaling mechanisms of ISGs in Mtb-infected human monocyte-derived Mϕs (hMDMs) and THP-1-derived Mϕs (THP-1-Mϕs). Among 28 of the detected ISGs, 90% of them exerted a significant increase in Mtb-infected Mϕs. Additionally, we found that cytosolic cyclic (GMP-AMP) synthase (cGAS), toll-like receptor-2 (TLR-2) and TLR-4 signaling pathways participated in ISG induction. Their downstream elements of TANK-binding kinase 1 (TBK1), nuclear factor-kappa B (NF-κB), mitogen-activated protein kinase (MAPK), and Janus kinase-signal transducer and activator of transcription (JAK-STAT) were selectively involved in Mtb-mediated ISG production. Finally, the numerous types of ISG expression in hMDMs of TB patients were more susceptible to restimulation of Mtb infection or/and IFN treatment than that of healthy people. Hence, different signaling pathways define different ISG expression during Mtb infection and this helps to illustrate how ISGs are elucidated and to better understand the host immune responses to Mtb infection in Mϕs.
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spelling pubmed-63870942019-02-27 Different Signaling Pathways Define Different Interferon-Stimulated Gene Expression during Mycobacteria Infection in Macrophages Zhou, Xinying Yang, Jiahui Zhang, Zelin Zhang, Lijie Zhu, Bo Lie, Linmiao Huang, Yubin Ma, Rui Zhou, Chaoying Hu, Shengfeng Wen, Qian Ma, Li Int J Mol Sci Article Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) represents one of the greatest threats to human health., Interferons (IFNs) in combination with the first-line of anti-TB drugs have been used for treating TB for decades in the clinic, but how Mtb infection regulates interferon-stimulated genes (ISGs) in human macrophages (Mϕs) remains unknown. In this study, we investigated the expression-signature and associated innate signaling mechanisms of ISGs in Mtb-infected human monocyte-derived Mϕs (hMDMs) and THP-1-derived Mϕs (THP-1-Mϕs). Among 28 of the detected ISGs, 90% of them exerted a significant increase in Mtb-infected Mϕs. Additionally, we found that cytosolic cyclic (GMP-AMP) synthase (cGAS), toll-like receptor-2 (TLR-2) and TLR-4 signaling pathways participated in ISG induction. Their downstream elements of TANK-binding kinase 1 (TBK1), nuclear factor-kappa B (NF-κB), mitogen-activated protein kinase (MAPK), and Janus kinase-signal transducer and activator of transcription (JAK-STAT) were selectively involved in Mtb-mediated ISG production. Finally, the numerous types of ISG expression in hMDMs of TB patients were more susceptible to restimulation of Mtb infection or/and IFN treatment than that of healthy people. Hence, different signaling pathways define different ISG expression during Mtb infection and this helps to illustrate how ISGs are elucidated and to better understand the host immune responses to Mtb infection in Mϕs. MDPI 2019-02-03 /pmc/articles/PMC6387094/ /pubmed/30717477 http://dx.doi.org/10.3390/ijms20030663 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Zhou, Xinying
Yang, Jiahui
Zhang, Zelin
Zhang, Lijie
Zhu, Bo
Lie, Linmiao
Huang, Yubin
Ma, Rui
Zhou, Chaoying
Hu, Shengfeng
Wen, Qian
Ma, Li
Different Signaling Pathways Define Different Interferon-Stimulated Gene Expression during Mycobacteria Infection in Macrophages
title Different Signaling Pathways Define Different Interferon-Stimulated Gene Expression during Mycobacteria Infection in Macrophages
title_full Different Signaling Pathways Define Different Interferon-Stimulated Gene Expression during Mycobacteria Infection in Macrophages
title_fullStr Different Signaling Pathways Define Different Interferon-Stimulated Gene Expression during Mycobacteria Infection in Macrophages
title_full_unstemmed Different Signaling Pathways Define Different Interferon-Stimulated Gene Expression during Mycobacteria Infection in Macrophages
title_short Different Signaling Pathways Define Different Interferon-Stimulated Gene Expression during Mycobacteria Infection in Macrophages
title_sort different signaling pathways define different interferon-stimulated gene expression during mycobacteria infection in macrophages
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6387094/
https://www.ncbi.nlm.nih.gov/pubmed/30717477
http://dx.doi.org/10.3390/ijms20030663
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