Understanding the Relationship between Glutathione, TGF-, and Vitamin D in Combating Mycobacterium tuberculosis Infections

Tuberculosis (TB) remains a pervasive global health threat. A significant proportion of the world's population that is affected by latent tuberculosis infection (LTBI) is at risk for reactivation and subsequent transmission to close contacts. Despite sustained efforts in eradication, the rise of multidrug-resistant strains ofMycobacteriumtuberculosis(M. tb) has rendered traditional antibiotic therapy less effective at mitigating the morbidity and mortality of the disease. Management of TB is further complicated by medications with various off-target effects and poor compliance. Immunocompromised patients are the most at-risk in reactivation of a LTBI, due to impairment in effector immune responses. Our laboratory has previously reported that individuals suffering from Type 2 Diabetes Mellitus (T2DM) and HIV exhibited compromised levels of the antioxidant glutathione (GSH). Restoring the levels of GSH resulted in improved control ofM. tbinfection. The goal of this review is to provide insights on the diverse roles of TGF- beta and vitamin D in altering the levels of GSH, granuloma formation, and clearance ofM. tbinfection. We propose that these pathways represent a potential avenue for future investigation and development of new TB treatment modalities.