Overview: A new angle on TB treatment
Tuberculosis (TB) continues to be a major global health challenge, affecting more than 10 million people annually with about 1.25 million deaths each year. While steroids such as dexamethasone are already used in selected TB cases, the precise impact of these drugs on immune cells has remained unclear. A recent study from Trinity College Dublin, based at St James’s Hospital in Dublin, offers new evidence that targeted steroid use could act as a universal complementary therapy. Published in Scientific Reports, the work explores how dexamethasone influences macrophages—the immune cells that play a central role in containing and clearing Mycobacterium tuberculosis (Mtb).
What the researchers did
To understand how dexamethasone affects the macrophage’s ability to fight TB, the team examined immune cells derived from the blood of healthy volunteers and macrophages recovered from lung fluid donated during routine bronchoscopies. By infecting these macrophages with Mtb in a controlled lab setting and then applying dexamethasone, the researchers could observe how the drug modulates the immune response and the fate of the bacteria inside the cells.
Key findings: balancing inflammation and antimicrobial defense
Several important discoveries emerged from the study. First, dexamethasone reduced glycolysis in both lung- and blood-derived macrophages. This effectively lowers the energy available to the cell, which can influence how aggressively the cell responds to infection. Second, the drug decreased the production of multiple cytokines, including IL-1β, TNF, IL-6, IL-8, and IL-10. While excessive inflammation can cause tissue damage, a controlled inflammatory response is essential for effective antimicrobial action. The researchers found that dexamethasone can help temper damaging inflammation while preserving, and in some cases enhancing, the macrophages’ ability to fight Mtb.
Crucially, Mtb-infected macrophages treated with dexamethasone showed reduced bacterial burden. The team identified autophagy and phagosomal acidification as part of the mechanism by which dexamethasone enhances the macrophage’s capacity to degrade and clear bacteria. In short, dexamethasone can both suppress harmful inflammation and bolster antimicrobial defenses, at least in certain macrophage populations.
Why tissue origin matters
The study revealed that macrophages from different tissue sources respond differently to glucocorticoids. This finding highlights the importance of tissue origin in shaping drug responses and could influence how targeted therapies are developed. It also marks one of the first studies to show that dexamethasone can reduce inflammatory signals while preserving or even increasing antimicrobial activity in primary human lung macrophages infected with Mtb.
Clinical implications: a potential shift in TB care
These results support the idea of using steroids as an adjunct to standard antimicrobials, particularly in TB cases marked by excessive inflammation. Steroids might also be beneficial alongside antimicrobials in preventive therapy to reduce progression from latent TB infection to active disease. While promising, the researchers emphasize that translating this into routine practice will require careful targeting to maintain antimicrobial defense while controlling inflammation.
Dr. Donal Cox, a senior research fellow at Trinity College Dublin, commented: “Our study shows that dexamethasone, known to dampen inflammation, can also help macrophages fight tuberculosis more effectively. This challenges the assumption that steroids always suppress immunity and opens the door to smarter, targeted adjunctive therapies that balance inflammation control with antimicrobial defense.”
Prof. Joseph Keane added: “In clinical practice, steroids are the most under-used adjunctive therapy for TB. This study provides new evidence to redefine steroid use in TB care—targeting inflammation without compromising antimicrobial defense.”
Looking ahead: smarter, targeted steroid therapies
The researchers are exploring ways to translate these findings into practical therapies, such as delivering steroids directly to lung macrophages via inhaled nanoparticles. They also aim to map how steroids alter metabolic pathways in lung macrophages versus blood-derived macrophages, with the goal of developing more precise, tissue-targeted treatments that maximize microbial killing while minimizing collateral damage.
What this could mean for patients
If future work confirms these benefits in clinical settings, targeted steroid therapies could help hasten recovery for TB patients, reduce lingering symptoms, and improve outcomes when used alongside standard antimicrobials. The work points toward a future where host-directed strategies balance inflammation control with robust antimicrobial defense, potentially changing the standard of care for TB around the world.
