Abstract
Mycobacterium tuberculosis (M. tb), a rod-shaped acid-fast bacterium, 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 has latent tuberculosis infection (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 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) that were derived from healthy subjects and testing their granulomatous effector responses against both M. bovis bacille Calmette-Guérin (BCG) and 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 L-GSH treatment can decrease the intracellular survival of both BCG and virulent M. tb, as well as downregulate the levels of overexpressed proinflammatory cytokines delegated from the granulomas derived from not only healthy subjects but also individuals with T2DM.