Turbocharging immune system could mean end of antibiotics

A remarkable new way to tackle deadly drug-resistant infections – by supercharging the body’s own immune cells rather than relying on new medicines – has been developed by scientists.

Antimicrobial resistance (AMR) – where bacteria, viruses, fungi and parasites no longer respond to drug treatments – has become one of the most serious health threats.

In Britain alone, it contributes to 35,000 deaths a year, says the patient charity AMR Action UK.

Common infections that are now resistant to many available medications include urinary tract infections, pneumonia, E.coli, MRSA and C.difficile. The problem has been worsened by the fact that few new antibiotics have been developed in decades.

In the new breakthrough approach, instead of trying to kill bacteria directly, researchers at Trinity College Dublin trained immune cells called macrophages to do it, by exposing them to interferon gamma, a protein the immune system produces naturally as an alert signal when the body is under attack.

As a result, the macrophages were able to fight off infections faster and more powerfully, reported the Journal of Clinical Investigation.

Macrophages, the body’s front line 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, told Good Health: ‘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 too.

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 – this is its rapid-response, first-line defence which reacts quickly to any threat, responding in the same way to all germs and foreign substances, but it usually has no memory, and so offers no lasting immunity to the pathogen.

This is different from the adaptive immune system, which is highly specialised – it learns from specific bugs and builds long-lasting immunity, using antibodies with a memory of particular infections. This is the system that vaccines target.

‘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 were able to improve the immune responses of these cells when they were infected with pathogens.

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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 currently 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 an 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.