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).
Keywords: BCG vaccination; M. tb; cytokines; glutathione; granulomas; immune exhaustion.