Metabolic Biomarker Distinguishes Latent from Active Tuberculosis and Tracks Treatment Response

Tuberculosis (TB) remains the world’s leading infectious killer, with 10.8 million cases and 1.25 million deaths recorded globally in 2023. Yet many infected individuals never develop active disease, underscoring gaps in understanding the host factors that determine protection versus progression. Clinical tools are needed to distinguish controlled infection from active disease and track treatment response. New findings now show that a metabolic biomarker in immune cells may help explain differential control of TB infection.

Trinity College Dublin researchers have identified an immune “energy signature” in circulating monocytes that differentiates latent TB infection from active disease. The signature reflects how these innate immune cells generate and use energy during host defense. The work centers on immunometabolism and links cellular energy pathways with antibacterial responsiveness.

In individuals with latent TB, monocytes remained metabolically flexible, a state associated with robust antibacterial activity. By contrast, monocytes from people with active TB showed impaired metabolism and weaker responses to infection. These functional differences indicate that immune-cell energy programs influence whether infection is contained or progresses.

The study, published in the Journal of Infection, focused on circulating monocytes and used single-cell metabolic profiling to compare latent infection with active disease. Investigators also observed that TB treatment could partially restore features of healthier immune-cell metabolism. These metabolic shifts may serve as correlates of protection and potential biomarkers of treatment response or disease recovery.

The work builds on growing international research into immunometabolism and provides one of the clearest comparisons to date between latent and active TB using single-cell metabolic profiling. By tying energy utilization to antibacterial readiness, the analysis outlines a measurable biological pattern linked to disease control. The authors note that the findings could help pave the way for improved TB monitoring tools.

“We found that the way immune cells generate and use energy appears to play an important role in determining whether TB remains controlled or progresses to active disease. In people with latent TB, these immune cells appear metabolically adaptable and ready to respond to infection. In active TB disease, however, the same cells show signs of dysfunction and are less capable of mounting an effective immune response. Latent TB is often thought of as a dormant state, but our findings show the immune system is actively working to keep infection under control,” said Dr. Gráinne Jameson, postdoctoral researcher in immunology at Trinity Translational Medicine Institute.

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