Redox Biomarkers in Asymptomatic Latent Human Tuberculosis: A Comparison With Active Disease

Abstract

Background The latent TB infection (LTBI) is an asymptomatic infection caused by Mycobacterium tuberculosis (M.bt). Previous studies have shown a host-protective role for Heme oxygenase-1 (HO-1) during Mtb infection and an important involvement of Glutathione peroxidase-4 (Gpx4) in the necrotic pathology of the disease. Furthermore, increasing evidence suggested a crucial role for Glutathione in the granulomatous response to M. tb infection, with altered GSH levels associated to decreased host resistance. The aim of this study was to provide additional tools for discriminating the pathologic TB state and the asymptomatic infection. Methods We analyzed the gene expression of HO-1 and Gpx4 enzymes in blood of subjects with LTBI, active TB and healthy controls, and we also measured blood levels of the reduced (GSH) and oxidized (GSSG) forms of glutathione, together with the evaluation of GCL expression, the gene responsible for the GSH de novo synthesis. Results Our findings highlight a shift of glutathione homeostasis towards a more reducing conditions in LTBI, and a different modulation of GSH-dependent genes and HO-1 expression respect to active TB. Conclusion This study can provide useful tools to understand the redox background that address the infection toward the asymptomatic or active disease.