TNF in Human Tuberculosis: A Double-Edged Sword

Abstract

TNF, a pleiotropic proinflammatory cytokine, is important for protective immunity and immunopathology during Mycobacterium tuberculosis (Mtb) infection, which causes tuberculosis (TB) in humans. TNF is produced primarily by phagocytes in the lungs during the early stages of Mtb infection and performs diverse physiological and pathological functions by binding to its receptors in a context-dependent manner. TNF is essential for granuloma formation, chronic infection prevention, and macrophage recruitment to and activation at the site of infection. In animal models, TNF, in cooperation with chemokines, contributes to the initiation, maintenance, and clearance of mycobacteria in granulomas. Although anti-TNF therapy is effective against immune diseases such as rheumatoid arthritis, it carries the risk of reactivating TB. Furthermore, TNF-associated inflammation contributes to cachexia in patients with TB. This review focuses on the multifaceted role of TNF in the pathogenesis and prevention of TB and underscores the importance of investigating the functions of TNF and its receptors in the establishment of protective immunity against and in the pathology of TB. Such investigations will facilitate the development of therapeutic strategies that target TNF signaling, which makes beneficial and detrimental contributions to the pathogenesis of TB.

A systematic review of the mechanism of action and potential medicinal value of codonopsis pilosula in diseases

“…These proinflammatory factors have a wide range of biological activities and help coordinate the body’s response to infections. TNF-α belongs to the TNF ligand superfamily, which is mainly secreted by macrophages and lymphocytes ( Yuk et al, 2024 ), and promotes the production and secretion of IL-1β and IL-6. TNF-α regulates imbalances in immune regulation ( Deng et al, 2020 ), inflammation ( Xu Q. et al, 2023 ), cancer ( Zhu et al, 2019 ), memory disorders ( Ren et al, 2022 ) and other diseases.…”

Host Cell Death and Modulation of Immune Response against Mycobacterium tuberculosis Infection

“…TNF promotes apoptosis and is a potent proinflammatory cytokine that recruits various immune cells, such as neutrophils and T cells, to the site of infection. While essential for containing the infection, excessive TNF production can lead to tissue damage and pathology associated with TB [ 20 ]. Furthermore, type II interferon IFN-γ, produced primarily by T cells and natural killer (NK) cells, is also crucial for the activation of macrophages, induction of antigen presentation by increasing the expression of major histocompatibility complex (MHC) molecules on macrophages, promoting the Th1 (T-helper 1) immune response, and promoting autophagy and enhancing the maturation of phagosomes, the vesicles in which macrophages contain ingested bacteria, leading to more effective fusion with lysosomes and destruction of the bacteria [ 21 , 22 , 23 ].…”