Abstract
Tuberculosis (TB) is a major health threat to the human population worldwide. The etiology of the disease is Mycobacterium tuberculosis (Mtb), a highly successful intracellular pathogen. It has the ability to manipulate the host immune response and to make the intracellular environment suitable for its survival. Many studies have addressed the interactions between the bacteria and the host immune cells as involving many immune mediators and other cellular players. Interferon-β (IFN-β) signaling is crucial for inducing the host innate immune response and it is an important determinant in the fate of mycobacterial infection. The role of IFN-β in protection against viral infections is well established and has been studied for decades, but its role in mycobacterial infections remains much more complicated and debatable. The involvement of IFN-β in immune evasion mechanisms adopted by Mtb has been an important area of investigation in recent years. These advances have widened our understanding of the pro-bacterial role of IFN-β in host–pathogen interactions. This pro-bacterial activity of IFN-β appears to be correlated with its anti-inflammatory characteristics, primarily by antagonizing the production and function of interleukin 1β (IL-1β) and interleukin 18 (IL-18) through increased interleukin 10 (IL-10) production and by inhibiting the nucleotide-binding domain and leucine-rich repeat protein-3 (NLRP3) inflammasome. Furthermore, it also fails to provoke a proper T helper 1 (Th1) response and reduces the expression of major histocompatibility complex II (MHC-II) and interferon-γ receptors (IFNGRs). Here we will review some studies to provide a paradigm for the induction, regulation, and role of IFN-β in mycobacterial infection. Indeed, recent studies suggest that IFN-β plays a role in Mtb survival in host cells and its downregulation may be a useful therapeutic strategy to control Mtb infection.
Highlights
Tuberculosis remains a major global health threat to both human and animal populations
The in vivo situation is certainly much more complex and the possible role of additional DNA sensors still remains unclear, it is believed that cyclic GMP–AMP synthase (cGAS) is a major player in the IFN-β signature associated with active TB [13,47]
Activated signal transducer and activator of transcription 1 (STAT1)/STAT2 link with interferon regulatory factor 9 (IRF9) to form IFN-stimulated gene factor-3 (ISGF3), which binds to IFN-stimulated response elements (ISREs) and upregulates IFN-β-stimulated genes (ISGs) [18]
Summary
Tuberculosis remains a major global health threat to both human and animal populations. Induction of IFN-β by Mtb and other members of the MTBC group is an important step for activation of innate immunity This process is mediated by the activation of pattern-recognition receptors (PRR) such as Toll-like receptors (TLR) and cytosolic receptors such as retinoid-inducible gene 1 (RIG-I) and melanoma differentiation-associated gene 5 (MDA5) [55,56,57]. Many other studies [68,69] have reported that cGAS is required for activating IFN-β production via the stimulator of interferon genes (STING)/TBK1/IRF3 pathway during Mtb and Legionella pneumophila infection of macrophages. Some studies [68,73] support a model in which Mtb triggers the STING/TBK1 pathway using the ESX-1 production system to interrupt phagosomal membranes and thereby allowing bacterial DNA access to cGAS in the cytosol These results reveal that the mechanism of IFN-β induction in mycobacterial infection is more complex than the already established models suggest. The in vivo situation is certainly much more complex and the possible role of additional DNA sensors (which may work in close coordination with cGAS to activate the innate immune response) still remains unclear, it is believed that cGAS is a major player in the IFN-β signature associated with active TB [13,47]
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