Abstract
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.
Highlights
Mycobacterium tuberculosis (Mtb) infection, the main cause of tuberculosis (TB), represents one of the most abundant infectious challenges to human health
We further demonstrated that different Mtb-induced interferon-stimulated genes (ISGs) were dependent on the key element downstream of cyclic (GMP-AMP) synthase-stimulator of interferon genes, toll-like receptor-2 (TLR-2) and/or -4 signaling pathways, diversely
We applied human monocyte-derived Mφs (hMDMs) and human cell line derived THP-1-Mφs to evaluate the effect of Mtb infection on ISG expression
Summary
Mycobacterium tuberculosis (Mtb) infection, the main cause of tuberculosis (TB), represents one of the most abundant infectious challenges to human health. Mtb infection spreads to almost one-third of the population globally, only 10% of latent infections develop active TB, mainly due to the effective innate and subsequent adaptive host immune responses [8]. Among these host defense mechanisms, macrophages (Mφs) represent the first line of anti-mycobacterial immune system, they serve as the predominant habitat for Mtb infection and proliferation at the same time [9]. Upon Mtb infection, in addition to phagocytic activity and ability to present antigens to T-cells, Mφs rapidly react by developing antimycobacterial immune response highly dependent on the production of cytokines, in particular IFNs [10]. In Mφs we investigated the effect and mechanism-of-action of Mtb infection on 28 ISG production responding to virus infection [11]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
