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).
Highlights
Tuberculosis (TB), caused by Mycobacterium tuberculosis (M. tb), continues to afflict millions of people worldwide
Individuals infected with M. tb have a 5–15% lifetime risk of developing an active disease; immunocompromised patients, such as people living with diabetes, malnutrition, human immunodeficiency virus (HIV), or those who use tobacco, have a higher risk of developing active TB [1]
M. tb infection occurs due to inhalation of infectious aerosolized droplets, and the bacteria become seeded in the lower respiratory tract where there is an enrichment of alveolar macrophages
Summary
Tuberculosis (TB), caused by Mycobacterium tuberculosis (M. tb), continues to afflict millions of people worldwide. In 2017, approximately 10 million people suffered from active TB and 1.6 million died from this disease [1]. One third of the world’s population is latently infected with M. tb. Individuals infected with M. tb have a 5–15% lifetime risk of developing an active disease; immunocompromised patients, such as people living with diabetes, malnutrition, human immunodeficiency virus (HIV), or those who use tobacco, have a higher risk of developing active TB [1]. Common symptoms of active pulmonary TB are coughs with a bloody sputum, chest pains, weakness, weight loss, fever, and night sweats, eventually resulting in death when untreated [1]. M. tb infection occurs due to inhalation of infectious aerosolized droplets, and the bacteria become seeded in the lower respiratory tract where there is an enrichment of alveolar macrophages
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
