Glutathione Modulates Efficacious Changes in the Immune Response against Tuberculosis Original paper

What was reviewed?

This review evaluated how glutathione modulates immune responses against Mycobacterium tuberculosis infection and how glutathione supplementation may function as an adjunctive therapy for tuberculosis. The authors examined the biochemical role of glutathione in redox balance, cytokine regulation, and immune cell metabolism during tuberculosis. The review emphasized how oxidative stress disrupts immune control of Mycobacterium tuberculosis and how glutathione restores effective host defense. It integrated mechanistic data on granuloma formation, macrophage antimicrobial activity, T-cell metabolism, and cytokine balance to explain why glutathione plays a central role in tuberculosis immunity.

Who was reviewed?

The review synthesized evidence from human clinical studies, animal models, and in vitro immune cell experiments. It included data from healthy individuals, tuberculosis patients, and high-risk populations such as people living with HIV and those with type 2 diabetes. The authors also reviewed studies involving macrophages, natural killer cells, T lymphocytes, and monocytes infected with Mycobacterium tuberculosis. No single cohort was analyzed. Instead, the review combined findings across multiple experimental systems to describe host–pathogen interactions under conditions of glutathione sufficiency and deficiency.

Most important findings

The review demonstrated that glutathione deficiency consistently associates with impaired immune control of Mycobacterium tuberculosis. Low glutathione levels increased oxidative stress and disrupted cytokine balance by suppressing Th1 cytokines such as IL-2, IL-12, IFN-γ, and TNF-α while increasing immunosuppressive cytokines, including IL-10 and TGF-β. These changes weakened macrophage killing, reduced nitric oxide production, and impaired granuloma integrity. The authors showed that glutathione directly inhibited the intracellular growth of Mycobacterium tuberculosis in macrophages and enhanced the antimicrobial activity of natural killer cells and T cells. In patients with HIV or diabetes, reduced expression of glutathione-synthesizing enzymes further worsens redox imbalance and susceptibility to tuberculosis. From a microbiome signatures perspective, Mycobacterium tuberculosis emerged as the dominant microbial driver, with host glutathione levels acting as a critical modifier of pathogen persistence rather than altering microbial diversity.

Key implications

This review identifies glutathione as a key immunomodulator rather than a passive antioxidant in tuberculosis. Restoring glutathione levels improves cytokine balance, strengthens cell-mediated immunity, and enhances antimicrobial defenses against Mycobacterium tuberculosis. The findings support glutathione or glutathione-precursor supplementation as a potential adjunct to standard tuberculosis therapy, especially in immunocompromised populations. For clinicians, assessing and correcting redox imbalance may improve treatment response, reduce disease severity, and lower relapse risk in tuberculosis patients.