Glutathione Modulates Efficacious Changes in the Immune Response Against Tuberculosis

Abnousian, Arbi; Vasquez, Joshua; Sasaninia, Kayvan; Kelley, Melissa; Venketaraman, Vishwanath

doi:10.20944/preprints202304.0166.v1

2023

DOI: 10.20944/preprints202304.0166.v1

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Glutathione Modulates Efficacious Changes in the Immune Response Against Tuberculosis

Arbi Abnousian¹,

Joshua Vasquez²,

Kayvan Sasaninia³

et al.

Abstract: Glutathione (GSH) is an antioxidant that our cells utilize to prevent damage done by reactive oxygen species, free radicals, peroxides, lipid peroxides, and heavy metals [1]. Due to its immune role in tuberculosis (TB), GSH is hypothesized to play an important part in the immune response against M. tb. Furthermore, one of the hallmark structures of TB is granuloma formation, which involves many types of immune cells. T cells specifically are a major component and are involved in the release of cytokines and ac… Show more

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2024

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Cited by 3 publications

References 75 publications

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Immune Responses to Mycobacterium tuberculosis Infection in the Liver of Diabetic Mice

Badaoui,

Sasaninia,

Mohan

et al. 2024

Biomedicines

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Individuals with uncontrolled diabetes are highly susceptible to tuberculosis (TB) caused by Mycobacterium tuberculosis (M. tb) infection. Novel treatments for TB are needed to address the increased antibiotic resistance and hepatoxicity. Previous studies showed that the administration of liposomal glutathione (L-GSH) can mitigate oxidative stress, bolster a granulomatous response, and diminish the M. tb burden in the lungs of M. tb-infected mice. Nonetheless, the impact of combining L-GSH with conventional TB treatment (RIF) on the cytokine levels and granuloma formation in the livers of diabetic mice remains unexplored. In this study, we evaluated hepatic cytokine profiles, GSH, and tissue pathologies in untreated and L-GSH, RIF, and L-GSH+RIF treated diabetic (db/db) M. tb-infected mice. Our results indicate that treatment of M. tb-infected db/db mice with L-GSH+RIF caused modulation in the levels of pro-inflammatory cytokines and GSH in the liver and mitigation in the granuloma size in hepatic tissue. Supplementation with L-GSH+RIF led to a decrease in the M. tb burden by mitigating oxidative stress, promoting the production of pro-inflammatory cytokines, and restoring the cytokine balance. These findings highlight the potential of L-GSH+RIF combination therapy for addressing active EPTB, offering valuable insights into innovative treatments for M. tb infections.

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Immune Responses to Mycobacterium tuberculosis Infection in the Liver of Diabetic Mice

Badaoui,

Sasaninia,

Mohan

et al. 2024

Biomedicines

Self Cite

View full text Add to dashboard Cite

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Immunopathology of Pulmonary Mycobacterium tuberculosis Infection in a Humanized Mouse Model

Kolloli,

Kumar,

Venketaraman

et al. 2024

IJMS

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Despite the availability of antibiotic therapy, tuberculosis (TB) is prevailing as a leading killer among human infectious diseases, which highlights the need for better intervention strategies to control TB. Several animal model systems, including mice, guinea pigs, rabbits, and non-human primates have been developed and explored to understand TB pathogenesis. Although each of these models contributes to our current understanding of host-Mycobacterium tuberculosis (Mtb) interactions, none of these models fully recapitulate the pathological spectrum of clinical TB seen in human patients. Recently, humanized mouse models are being developed to improvise the limitations associated with the standard mouse model of TB, including lack of necrotic caseation of granulomas, a pathological hallmark of TB in humans. However, the spatial immunopathology of pulmonary TB in humanized mice is not fully understood. In this study, using a novel humanized mouse model, we evaluated the spatial immunopathology of pulmonary Mtb infection with a low-dose inoculum. Humanized NOD/LtSscidIL2Rγ null mice containing human fetal liver, thymus, and hematopoietic CD34+ cells and treated with human cytokines were aerosol challenged to implant <50 pathogenic Mtb (low dose) in the lungs. At 2 and 4 weeks post infection, the tissue bacterial load, disease pathology, and spatial immunohistology were determined in the lungs, liver, spleen, and adipose tissue using bacteriological, histopathological, and immunohistochemical techniques. The results indicate that implantation of <50 bacteria can establish a progressive disease in the lungs that transmits to other tissues over time. The disease pathology in organs correspondingly increased with the bacterial load. A distinct spatial distribution of T cells, macrophages, and natural killer cells were noted in the lung granulomas. The kinetics of spatial immune cell distribution were consistent with the disease pathology in the lungs. Thus, the novel humanized model recapitulates several key features of human pulmonary TB granulomatous response and can be a useful preclinical tool to evaluate potential anti-TB drugs and vaccines.

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The Role of Glutathione in the Management of Cell-Mediated Immune Responses in Individuals with HIV

Lin,

Erdos,

Louie

et al. 2024

IJMS

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Human immunodeficiency virus (HIV) is a major cause of death worldwide. Without appropriate antiretroviral therapy, the infection can develop into acquired immunodeficiency syndrome (AIDS). AIDS leads to the dysregulation of cell-mediated immunity resulting in increased susceptibility to opportunistic infections and excessive amounts of inflammatory cytokines. HIV-positive individuals also demonstrate diminished glutathione (GSH) levels which allows for increased viral replication and increased pro-inflammatory cytokine release, further contributing to the high rates of mortality seen in patients with HIV. Adequate GSH supplementation has reduced inflammation and slowed the decline of CD4+ T cell counts in HIV-positive individuals. We aim to review the current literature regarding the role of GSH in cell-mediated immune responses in individuals with HIV- and AIDS-defining illnesses.

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Glutathione Modulates Efficacious Changes in the Immune Response Against Tuberculosis

Cited by 3 publications

References 75 publications

Immune Responses to Mycobacterium tuberculosis Infection in the Liver of Diabetic Mice

Immune Responses to Mycobacterium tuberculosis Infection in the Liver of Diabetic Mice

Immunopathology of Pulmonary Mycobacterium tuberculosis Infection in a Humanized Mouse Model

The Role of Glutathione in the Management of Cell-Mediated Immune Responses in Individuals with HIV

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