Study Finds Immune Cell Metabolism Differs Between Latent and Active TB

Tuberculosis infects millions of people each year, yet not everyone who carries the bacterium becomes ill. Why some individuals keep the infection in check while others progress to active disease has long been an open question. A new study from Trinity College Dublin points to cellular metabolism—how immune cells generate and use energy—as a key factor in that difference.

Published in the Journal of Infection, the new study focused on circulating monocytes, immune cells that play a central role in the body's defense against TB. The researchers compared monocytes from people with latent TB, where infection is controlled, to those from people with active TB disease, and found meaningful differences in how those cells function metabolically.

"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," said lead author Gráinne Jameson. "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."

TB remains the world's leading infectious killer, with 10.8 million cases and 1.25 million deaths recorded globally in 2023. The study adds to a growing body of research into immunometabolism—the relationship between immune function and cellular energy use—while offering one of the clearest comparisons to date between latent and active TB using single-cell metabolic profiling.

The study also found that TB treatment could partially restore healthier immune cell metabolism, raising the possibility that these metabolic changes could serve as biomarkers of treatment response or disease recovery—something clinicians currently lack reliable tools to measure in real time.

"Our findings suggest that immune metabolism could potentially help us monitor treatment response more precisely and, in the future, may even support more personalized treatment approaches," said senior author Sharee Basdeo.

The research team plans to conduct larger longitudinal studies tracking patients before, during, and after treatment to determine whether immune metabolism can predict long-term outcomes and treatment success.