Effects of NAC and L-GSH in enhancing granulomatous responses against mycobacterial infections

Mycobacterium tuberculosis (M. tb), a rod-shaped, acid-fast bacteria, is the causative agent of tuberculosis (TB). TB remains one of the leading causes of morbidity and mortality worldwide. Additionally, approximately one-third of the world’s population is latently infected with M. tb (LTBI) as a result of the body’s primary mechanism of defense against M. tb infection, the formation of a granuloma. A granuloma is the aggregation of immune cells that encapsulate the bacteria to keep them localized to prevent further infection and thus the bacteria become quiescent. However, if an individual becomes immunocompromised, they become more susceptible to M. tb, which may lead to bacterial reactivation and an active infection, because the host is no longer able to generate adequate immune responses. In this study, we examined N-acetyl-cysteine (NAC, a precursor to glutathione (GSH)) and liposomal glutathione’s (L-GSH) effectiveness in promoting the formation of solid, stable granulomas. We assessed this ability by generating in vitro human granulomas constructed from peripheral blood mononuclear cells (PBMCs) which were derived from healthy subjects and tested their granulomatous effector responses against the highly virulent Erdman strain of M. tb. Additionally, we measured the survival and immune characteristics of the Erdman strain of M. tb in THP-1 originated macrophages as well as in vitro granulomas generated from individuals from type 2 diabetes (T2DM). Our results demonstrate that NAC and L-GSH treatments can decrease the intracellular survival of virulent M. tb, as well as downregulate the levels of overexpressed pro-inflammatory cytokines delegated from the granulomas derived from not only healthy subjects but individuals with T2DM.