Elucidating the Efficacy of the Bacille Calmette–Guérin Vaccination in Conjunction with First Line Antibiotics and Liposomal Glutathione

Abstract

Mycobacterium tuberculosis (M. tb) is the etiological agent that is responsible for causing tuberculosis (TB). Although every year M. tb infection affects millions of people worldwide, the only vaccine that is currently available is the Bacille Calmette–Guérin (BCG) vaccine. However, the BCG vaccine has varying efficacy. Additionally, the first line antibiotics administered to patients with active TB often cause severe complications and side effects. To improve upon the host response mechanism in containing M. tb infection, our lab has previously shown that the addition of the biological antioxidant glutathione (GSH) has profound antimycobacterial effects. The aim of this study is to understand the additive effects of BCG vaccination and ex-vivo GSH enhancement in improving the immune responses against M. tb in both groups; specifically, their ability to mount an effective immune response against M. tb infection, maintain CD4+ and CD8+ T cells in the granulomas, their response to liposomal glutathione (L-GSH), with varying suboptimal levels of the first line antibiotics isoniazid (INH) and pyrazinamide (PZA), the expressions of programmed death receptor 1 (PD-1), and their ability to induce autophagy. Our results revealed that BCG vaccination, along with GSH enhancement, can prevent the loss of CD4+ and CD8+ T cells in the granulomas and improve the control of M. tb infection by decreasing the expressions of PD-1 and increasing autophagy and production of the cytokines interferon gamma IFN-γ and tumor necrosis factor-α (TNF-α).

Effects of Oral Liposomal Glutathione in Altering the Immune Responses Against Mycobacterium tuberculosis and the Mycobacterium bovis BCG Strain in Individuals With Type 2 Diabetes

“…This measurement was used to investigate the efficacy of using 1/10 of the MIC of PZA and INH in controlling M. tb infection within in vitro granulomas inT2DM group, with the basis coming from a previous finding in our lab that showed MIC of PZA and INH was able to reduce M. tb . burden in healthy individuals ( Abrahem et al., 2019 ). However the efficacy of these antibiotics at 1/10 MIC against M.tb in individuals with T2DM was not previously determined.…”

Cyclic Peptide [R4W4] in Improving the Ability of First-Line Antibiotics to Inhibit Mycobacterium tuberculosis Inside in vitro Human Granulomas

“…It has been reported that autophagy functionally benefits some diseases such as cancer, cardiomyopathy, diabetes, liver disease, and infections ( 29 – 31 ). LC3B is a mammalian homolog of the yeast ATG8 protein, which is a ubiquitin-like protein related to autophagosomal membranes ( 32 , 33 ). Therefore, LC3B is an important and direct marker used for detecting autophagy levels ( 32 , 33 ).…”

“…LC3B is a mammalian homolog of the yeast ATG8 protein, which is a ubiquitin-like protein related to autophagosomal membranes ( 32 , 33 ). Therefore, LC3B is an important and direct marker used for detecting autophagy levels ( 32 , 33 ). The LC3B protein in the granulomas were stained by an anti-LC3B antibody tagged with PE, a red fluorescent dye.…”

The Role of Dendritic Cells in TB and HIV Infection

“…Furthermore, in vitro glutathione (GSH) treatment of immune cells isolated from Mycobacterium bovis Bacille Calmette-Guérin (BCG) vaccine subjects improves the immune response and clearance of the M. tb [ 65 ]. GSH treatment has been shown to increase production of the cytokines IFN-γ and TNF-α, resulting in enhanced effector functions of macrophages, natural killer cells, and CD8+ T-cells.…”