Glutathione Depletion Exacerbates Hepatic Mycobacterium tuberculosis Infection Original paper

What was studied?

This study examined how glutathione depletion alters host immune control of extrapulmonary Mycobacterium tuberculosis infection, with a focus on the liver and spleen. The authors investigated whether reduced glutathione levels worsen oxidative stress, disrupt cytokine signaling, impair granuloma structure, and increase bacterial burden during hepatic tuberculosis. The work used a controlled murine infection model to isolate the immunological effects of glutathione loss during active infection. The focus keyphrase glutathione depletion in hepatic tuberculosis applies directly to this investigation, as the study centered on how glutathione depletion in hepatic tuberculosis shapes immune dysfunction and bacterial survival.

Who was studied?

The study used wild-type C57BL/6 mice infected with the virulent Mycobacterium tuberculosis H37Rv strain via aerosol exposure. The researchers induced glutathione depletion using diethyl maleate and compared treated mice with untreated infected controls over two, four, and eight weeks. The analysis focused on hepatic and splenic tissues, measuring bacterial load, oxidative stress markers, cytokine production, and granuloma architecture. No human participants were involved, and all findings reflect host–pathogen interactions in a mammalian model relevant to extrapulmonary tuberculosis.

Most important findings

Glutathione depletion markedly worsened hepatic tuberculosis outcomes. Treated mice showed sharp reductions in reduced glutathione with parallel increases in oxidized glutathione and malondialdehyde, confirming severe oxidative stress. These changes correlated with higher Mycobacterium tuberculosis burden in both liver and spleen. Cytokine signaling shifted toward immune dysregulation, with reduced IL-12 and IL-17, elevated IL-6, TNF-α, IFN-γ, and strong upregulation of TGF-β. Granulomas became large, diffuse, and poorly organized, indicating impaired containment of the pathogen. From a microbiome perspective, the study identified Mycobacterium tuberculosis as the dominant microbial driver, showing that host redox imbalance directly enhances intracellular bacterial survival rather than altering microbial diversity.

Key implications

The findings establish glutathione as a critical regulator of immune control in extrapulmonary tuberculosis. Loss of glutathione promotes oxidative stress, suppresses effective granuloma maturation, and enables Mycobacterium tuberculosis persistence despite elevated inflammatory signals. For clinicians, this work supports glutathione status as a potential modifier of tuberculosis severity, especially in immunocompromised states such as HIV or diabetes. Therapeutic strategies that restore glutathione homeostasis may strengthen host defense and improve outcomes in hepatic and disseminated tuberculosis.