Scientists at Trinity College Dublin have developed a novel immune therapy aimed at combating drug-resistant infections by enhancing the body’s own immune defenses rather than relying on new antibiotics. The research addresses the growing global health threat of antimicrobial resistance (AMR), which occurs when bacteria, viruses, fungi, and parasites no longer respond to existing medications. In the United Kingdom, AMR contributes to approximately 35,000 deaths annually, according to the patient charity AMR Action UK.

The researchers focused on a type of white blood cell known as macrophages, which serve as a first line of defense by engulfing and destroying pathogens. By exposing these cells to interferon gamma—a protein naturally produced by the immune system to signal infection—the team “trained” the macrophages to respond more rapidly and aggressively to infection. This enhanced activation enabled the macrophages to more effectively kill dangerous drug-resistant bacteria, including Staphylococcus aureus, a common cause of skin and bloodstream infections, as well as the bacteria responsible for tuberculosis (TB).

Lead immunologist Dearbhla Murphy said that the study, published in the Journal of Clinical Investigation, builds on prior research into vaccine-induced immune responses. “We observed that macrophages trained with interferon gamma were better able to kill tuberculosis and S. aureus bacteria,” she stated. The concept is inspired by findings that certain vaccines, such as the TB vaccine, not only protect against targeted diseases but may also reduce mortality from other infections, suggesting an enhanced innate immune response.

Unlike adaptive immunity, which provides pathogen-specific memory and is the basis for traditional vaccines, this approach seeks to strengthen the innate immune system’s rapid but non-specific response. Murphy described this phenomenon as “trained immunity,” whereby the innate immune cells gain improved functional capacity based on previous exposure to signaling molecules like interferon gamma.

The research team also tested the therapy on immune cells from patients with genetic susceptibilities to infection and found that the enhanced immune response could overcome these vulnerabilities. Future research aims to determine whether this training method could extend protection against fungi and viruses in addition to bacteria.

Interferon gamma is already administered intravenously in clinical settings, particularly for patients with sepsis, suggesting potential for integration with existing treatments. Murphy indicated that in the future, the therapy might serve as a co-treatment alongside antibiotics for individuals infected with drug-resistant pathogens.

However, experts urge caution given the early stage of the research. Jenna Macciochi, an immunologist at the University of Sussex, described the findings as biologically plausible but emphasized the risk of excessive immune activation, which can cause inflammation or tissue damage. She noted that interferon gamma therapies have been associated with side effects such as flu-like symptoms and may exacerbate autoimmune conditions in some patients.

Despite these concerns, proponents see promise in the broader strategy of host-directed therapies, which aim to empower the body’s own defenses rather than solely attacking pathogens directly. Louise Nicholas, head of operations at AMR Action UK, welcomed the development as a potential avenue to reduce reliance on antibiotics and improve patient outcomes in the fight against resistant infections.