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

Institute of Molecular Immunology, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou 510515, China
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2019, 20(3), 663;
Received: 24 January 2019 / Revised: 31 January 2019 / Accepted: 31 January 2019 / Published: 3 February 2019
(This article belongs to the Section Molecular Microbiology)
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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. View Full-Text
Keywords: Mycobacterium tuberculosis (Mtb); interferon-stimulated genes (ISGs); macrophages (Mϕs); signaling pathways Mycobacterium tuberculosis (Mtb); interferon-stimulated genes (ISGs); macrophages (Mϕs); signaling pathways

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Zhou, X.; Yang, J.; Zhang, Z.; Zhang, L.; Zhu, B.; Lie, L.; Huang, Y.; Ma, R.; Zhou, C.; Hu, S.; Wen, Q.; Ma, L. Different Signaling Pathways Define Different Interferon-Stimulated Gene Expression during Mycobacteria Infection in Macrophages. Int. J. Mol. Sci. 2019, 20, 663.

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