Liposomal Glutathione Helps to Mitigate Mycobacterium tuberculosis Infection in the Lungs

Abstract

Mycobacterium tuberculosis (M. tb), the causative agent of tuberculosis (TB), is responsible for causing significant morbidity and mortality, especially among individuals with compromised immune systems. We have previously shown that the supplementation of liposomal glutathione (L-GSH) reduces M. tb viability and enhances a Th-1 cytokine response, promoting granuloma formation in human peripheral blood mononuclear cells in vitro. However, the effects of L-GSH supplementation in modulating the immune responses in the lungs during an active M. tb infection have yet to be explored. In this article, we report the effects of L-GSH supplementation during an active M. tb infection in a mouse model of pulmonary infection. We determine the total GSH levels, malondialdehyde (MDA) levels, cytokine profiles, granuloma formation, and M. tb burden in untreated and L-GSH-treated mice over time. In 40 mM L-GSH-supplemented mice, an increase in the total GSH levels was observed in the lungs. When compared to untreated mice, the treatment of M. tb-infected mice with 40 mM and 80 mM L-GSH resulted in a reduction in MDA levels in the lungs. L-GSH treatment also resulted in a significant increase in the levels of IL-12, IFN-γ, IL-2, IL-17, and TNF-α in the lungs, while down-regulating the production of IL-6, IL-10, and TGF-β in the lungs. A reduction in M. tb survival along with a decrease in granuloma size in the lungs of M. tb-infected mice was observed after L-GSH treatment. Our results show that the supplementation of mice with L-GSH led to increased levels of total GSH, which is associated with reduced oxidative stress, increased levels of granuloma-promoting cytokines, and decreased M. tb burden in the lung. These results illustrate how GSH can help mitigate M. tb infection and provide an insight into future therapeutic interventions.

Liposomal Glutathione Augments Immune Defenses against Respiratory Syncytial Virus in Neonatal Mice Exposed in Utero to Ethanol

“…One strategy for GSH supplementation during oxidant stress is oral LGSH, which has been shown to decrease oxidant stress in HIV subjects and patients with type 2 diabetes [32][33][34]. In a mouse model of an active Mycobacterium tuberculosis infection, GSH depletion exacerbated the pathogen burden, but oral LGSH decreased both pulmonary oxidant stress and granuloma-promoting immune responses, resulting in decreases in the pulmonary bacterial infection [58]. Similar results were obtained in a diabetic mouse model with an active Mycobacterium tuberculosis infection, demonstrating that oral LGSH treatments can also improve bacterial clearance in an immunocompromised model [59].…”

Comparative study of subcutaneous, intramuscular, and oral administration of bovine pathogenic Escherichia coli bacterial ghost vaccine in mice

“…Th1 activated mononuclear phagocytes (MP) as well as produced IL-12 to promote Th1-type cellular immune responses ( 52 ). IL-12, a polarizing cytokine, induces CD4 T cells to differentiate into a Th1 subset by two-stage differentiation a) IL-12 induces the outgrowth of IFN-γ Th1 cells, b) about half of Th1 cells ultimately gain CX3CR1 expression and exhibit a cytotoxic effector profile depending on the transcription factor ZEB2, which, in turn, produces IL-2 and IFN-γ ( 53 , 54 ). IFN-γ-dependent macrophage activation is important for bactericidal functions.…”

Host-directed therapy against mycobacterium tuberculosis infections with diabetes mellitus

“…Kachour et al. verified the therapeutic effects of L-GSH supplementation in a mouse model of tuberculosis, as manifested by a reduction in MTB burden and oxidative stress levels in the lungs, as well as an increase in lung levels of IL-12, IFN-γ, IL-2, IL-17, and TNF-α, and a decrease in IL-6, IL-10, and TGF-β production ( 196 ). Sasaninia et al.…”