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

Abstract

Latent tuberculosis infection is an asymptomatic infection caused by Mycobacterium tuberculosis. Previous studies have shown a host-protective role for heme oxygenase-1 (HO-1) during M. tuberculosis infection and an important involvement of glutathione peroxidase-4 (Gpx4) in the necrotic pathology of the disease. Furthermore, increasing evidence suggesting a crucial role for glutathione (GSH) in the granulomatous response to M. tuberculosis infection, with altered GSH levels associated with decreased host resistance. The aim of this study was to provide additional tools for discriminating between the pathologic tuberculosis state and asymptomatic infection. We analyzed the expression of genes coding for HO-1 and GPX4 enzymes in blood of subjects with latent tuberculosis infection, active tuberculosis, and healthy controls, and we also measured blood levels of the reduced (GSH) and oxidized (GSSG) forms of glutathione, together with evaluation of GCL coding gene expression, responsible for GSH de novo synthesis. Our findings highlight a shift in glutathione homeostasis towards a more reducing conditions in latent tuberculosis infection, and a different modulation of GSH-dependent genes and HO-1 expression compared to active tuberculosis. This study provides useful tools to understand the redox background that directs the infection toward the asymptomatic or active disease.