Role of Glutathione in Macrophage Control of Mycobacteria

Abstract

Reactive oxygen and nitrogen intermediates are important antimicrobial defense mechanisms of macrophages and other phagocytic cells. While reactive nitrogen intermediates have been shown to play an important role in tuberculosis control in the murine system, their role in human disease is not clearly established. Glutathione, a tripeptide and antioxidant, is synthesized at high levels by cells during reactive oxygen intermediate and nitrogen intermediate production. Glutathione has been recently shown to play an important role in apoptosis and to regulate antigen-presenting-cell functions. Glutathione also serves as a carrier molecule for nitric oxide, in the form ofS-nitrosoglutathione. Previous work from this laboratory has shown that glutathione andS-nitrosoglutathione are directly toxic to mycobacteria. A mutant strain ofMycobacterium bovisBCG, defective in the transport of small peptides such as glutathione, is resistant to the toxic effect of glutathione andS-nitrosoglutathione. Using the peptide transport mutant as a tool, we investigated the role of glutathione andS-nitrosoglutathione in animal and human macrophages in controlling intracellular mycobacterial growth.