Immune Cell Metabolism May Determine Tuberculosis Disease Progression

Researchers at Trinity College Dublin have identified key differences in how immune cells generate and use energy, a process known as cellular metabolism, in people with latent versus active tuberculosis (TB). 

The findings offer new insights into why some individuals control infection while others develop disease. 

The study, published in the Journal of Infection, focused on circulating monocytes, key immune cells involved in the defense against TB infection. The researchers found that cells from people with latent TB remain metabolically flexible, allowing them to mount strong antibacterial responses, whereas cells from people with active TB disease show impaired metabolism and weaker responses to infection.

TB remains the world's leading infectious killer, with 10.8 million cases and 1.25 million deaths recorded globally in 2023. While many people infected with Mycobacterium tuberculosis never become ill, researchers still do not fully understand why some individuals progress to active disease while others successfully control the infection. The findings could help pave the way for improved TB monitoring tools and future therapies or vaccines that target how immune cells generate energy.

Lead author Dr Gráinne Jameson, postdoctoral researcher in immunology at Trinity Translational Medicine Institute, said:

"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."

The study also found that TB treatment could partially restore healthier immune cell metabolism, suggesting these metabolic changes may eventually serve as a correlate of protection as well as biomarkers of treatment response or disease recovery.

Current TB treatment is lengthy and difficult, and clinicians still lack reliable tools to measure how well treatment is working 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."

Dr. Sharee Basdeo, Principal Investigator

The study builds on growing international research into immunometabolism, the relationship between immune function and cellular energy use, while providing one of the clearest comparisons to date between latent and active TB infection using single-cell metabolic profiling.

The researchers now plan to conduct larger longitudinal studies tracking patients before, during and after treatment to determine whether immune metabolism can predict long-term patient outcomes and treatment success.