A groundbreaking approach to combat deadly drug-resistant infections has been developed by scientists, focusing on supercharging the body's own immune cells rather than relying on new medications. Antimicrobial resistance (AMR), where bacteria, viruses, fungi, and parasites no longer respond to drug treatments, has become one of the most serious health threats globally. In Britain alone, it contributes to 35,000 deaths annually, according to the patient charity AMR Action UK.
Common infections now resistant to many available medications include urinary tract infections, pneumonia, E.coli, MRSA, and C.difficile. The problem has been exacerbated by the fact that few new antibiotics have been developed in recent decades. In this innovative approach, researchers at Trinity College Dublin trained immune cells called macrophages to kill bacteria more effectively, rather than trying to kill the bacteria directly. They did this by exposing macrophages to interferon gamma, a protein the immune system naturally produces as an alert signal when the body is under attack.
The results, published in the Journal of Clinical Investigation, showed that trained macrophages were able to fight off infections faster and more powerfully. Macrophages, the body's frontline foot soldiers against infection, are a type of white blood cell that work by engulfing and destroying bacteria, viruses, and other foreign invaders. After training with interferon gamma, they reacted faster, responded more strongly, and killed microbes far more effectively.
The research team tested their supercharged immune cells against some of the most dangerous drug-resistant Staphylococcus aureus bacteria, which causes skin infections and life-threatening bloodstream infections, as well as against tuberculosis (TB). Lead researcher Dearbhla Murphy, an immunologist at Trinity College Dublin, stated: 'When we had trained the cells, they were better able to kill tuberculosis and S. aureus bacteria.'
The inspiration came from previous research into Covid-19 and TB vaccines, which had shown that certain genes in the immune system were switched on by interferon gamma. Intriguingly, people vaccinated against TB were less likely to die not just from TB, but from other infections as well. The Trinity team wanted to know whether they could replicate that protective effect without a vaccine.
The new approach aims to support the body's innate immune system, its rapid-response, first-line defence which reacts quickly to any threat, responding in the same way to all germs and foreign substances, but usually has no memory and offers no lasting immunity to the pathogen. This is different from the adaptive immune system, which is highly specialised, learns from specific bugs, and builds long-lasting immunity using antibodies with a memory of particular infections. Vaccines target the adaptive system.
'Trained immunity [as with the new approach] is a way of strengthening the body's innate immune system so that it can learn from past infections and respond better the next time,' says Dr Murphy. 'What's so exciting is that we are reusing something the body makes naturally itself. And because we've used it successfully against two types of bacteria, it could potentially work against fungi and viruses.'
Crucially, the team also tested their approach on cells in a lab taken from patients with genetic mutations that made them more vulnerable to infections, and they were able to improve the immune responses of these cells when infected with pathogens. One of the next steps for the Trinity College researchers is to test whether training with interferon gamma can help kill infections caused by fungi and viruses as well as bacteria.
Dr Murphy says the treatment could one day be used alongside existing medicines as a co-therapy for people battling drug-resistant infections. Interferon gamma is already used in hospitals, given intravenously to patients with sepsis. It is possible that a drug version could be developed. However, experts urge caution.
Jenna Macciochi, an immunologist and honorary lecturer at the University of Sussex, described the research as biologically sound but stressed it remains at an early, laboratory-based stage. 'Interferon gamma is a naturally occurring immune-signalling molecule, but if you amplify immune activity too much, there is potential for excessive inflammation or tissue damage,' she says. In clinical settings, interferon gamma therapies have previously been linked to side-effects including flu-like symptoms, fatigue, fever, headaches, and muscle aches. There could also be risks of triggering or worsening autoimmune conditions in some patients.
Dr Macciochi says the approach could be part of a promising broader movement towards so-called host-directed therapies, treatments that help the body fight infection in smarter, more targeted ways. Louise Nicholas, head of operations at the charity AMR Action UK, welcomed the research. 'Exploring ways to support the body's own ability to fight infection could, over time, lead to more effective and longer-lasting solutions for patients, while reducing our reliance on antibiotics,' she says.
