Tuberculosis (TB) remains one of the leading causes of morbidity and mortality worldwide, while response to the only available vaccine (BCG) varies widely with a number of factors. In the majority of cases, TB infection in otherwise healthy individuals is rendered latent by the formation for granulomas. Individuals with latent TB granulomas are healthy and asymptomatic, however these latent infections can be reactivated at any point, especially if the individual becomes immunocompromised for any reason. Reactive oxygen species (ROS) including reduced glutathione can significantly contribute to control of TB infection during the initial stages. However, long term oxidative stress can damage cells, predisposing those with latent TB to reactivation of the disease.
A recent paper by Islamoglu et al. examined the ability of exogenously added glutathione to alter the granulomatous response to TB infection. Previous work has shown that reduced glutathione has direct antimycobacterial effects and can enhance the ability of natural killer and T cells to control TB. In this work exogenous glutathione was added to TB infected macrophages as L-GSH, a liposomal preparation of reduced glutathione shown to be readily taken up by cells. Total and oxidized glutathione were quantitated in granuloma lysates with and without treatment by L-GSH using the Arbor Assays DetectX® Glutathione Colorimetric Detection Kit (K006-H) and compared to total protein concentration. Statistically significant higher levels of glutathione per mg protein were detected after L-GSH treatment. IFN-gamma, TNF-alpha and IL-6 levels in granulomas were also measured with and without L-GSH treatment with INF-gamma increasing after L-GSH treatment and TNF-alpha and IL-6 levels decreasing.
Immunocompromising diseases such as HIV or type II diabetes negatively affect intracellular levels of glutathione and further compromise levels of enzymes involved in the synthesis and regulation of glutathione. This reduction in available ROS can make it harder for these individuals to suppress initial TB infection, and can also disrupt existing granulomas allowing the reactivation of latent TB and the emergence of active TB disease in individuals who had previously been asymptomatic. Islamoglu et al. demonstrated that restoring typical glutathione levels via treatment with L-GSH not only restored redox balance but also induced cytokines, and improved control of TB infection both in culture and in patients. This result highlights the importance of appropriate redox balance to immune response, and suggests that for individuals with at least some types of compromised immune systems, monitoring and if necessary supplementing reduced glutathione may improve their ability to control infection in disease like TB.