Researchers offer an exciting treatment to target the host, and not the bacteria

Posted on: 24 March 2026

As antibiotic resistance continues to rise worldwide, scientists are searching for new strategies to combat infections. This latest research at Trinity Translational Medicine Institute at Trinity College Dublin combats this problem by focusing on strengthening an individual’s own defence systems rather than relying solely on antimicrobial drugs. This approach aims to boost immune function to help clear infections more effectively. The study is published on World TB Day in the journal JCI Insight.  

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The team from the Basdeo Lab targeted the immune cells rather than the bacteria to help fight infections using a process called ‘trained immunity’. The team trained macrophages with the “alert signal” IFN-gamma (IFN-y), and they were better able to kill dangerous bacteria like methicillin-resistant S. aureus (MRSA) or the bacteria that causes tuberculosis (TB; M. tuberculosis).

Macrophages are immune cells that act like “clean-up crews,” that find, engulf, and destroy harmful microbes. Trained immunity is a way the body’s early (innate) immune system can “learn” from past infections and respond better the next time. Certain immune cells (like macrophages) are “reprogrammed” so that they react faster, respond more stronglyand they kill microbes more effectively. So, training could be used to help people who are more vulnerable to infection.

Next, when the team trained macrophages from individuals with a genetic mutation that would ordinarily result in increased susceptibility to infections, they were able to improve the macrophage's ability to kill MRSA. The team now believe that training could be used to help people who are more vulnerable to infection.

It is exciting as it is a treatment that targets the host and not the bacteria so it could likely work against a number of different bacteria and potentially viruses or fungi.

Key findings

• A single-dose of IFN-γ, an immune protein, was able to train macrophages.
• IFN-γ trained macrophages underwent epigenetic changes (changing how their DNA is organised), making infection-fighting genes easier to access and use.
• When undergoing training, macrophages used glutamine as a key fuel source.
• When exposed to bacteria like M. tuberculosis or MRSA, IFN-γ trained macrophages:
• Produced stronger signals that activate and attract other immune cells when exposed to bacteria.
• Enhanced their rate of glycolysis (the break down glucose into energy).
• Produced more reactive oxygen species (ROS), a bleach made by cells to kill bacteria.
• Were better at killing bacteria.
• The improved bacterial killing resulting from IFN-γ training depends on ROS, as IFN-γ trained macrophages from a patient with a genetic mutation that leaves them unable to make ROS, did not enhance MRSA killing.
• Finally, the team collected blood from donors who have a genetic mutation which leaves them more susceptible to infection. IFN-γ training macrophages from these donors resulted in better production of cytokines in response to M. tuberculosis, and an enhanced ability to kill MRSA.

Dr Dearbhla Murphy, postdoctoral research fellow and lead author

“This work is particularly exciting because it tackles antimicrobial resistance by targeting the host rather than the bacteria, meaning it could be effective against a range of drug-resistant pathogens. Crucially, we observed this training effect in cells from individuals who are typically more susceptible to infection, suggesting that immune training could help strengthen responses in vulnerable individuals.”

Dr Sharee Basdeo, Assistant Professor in the School of Medicine, and senior author, added: 

“ Our innate immune response is so crucial in the fight against TB. It dictates whether or not you become sick with the disease. This study is exciting because it shows that we can boost the function of a key innate immune cell - a macrophage - by training it with IFN-γ. This makes the macrophage faster and stronger at responding when it becomes infected.  

“TB remains the number one cause of death from an infection, with over a million people dying of TB every year worldwide. TB is very difficult to treat, and this is getting harder because of antibiotic resistant TB. Our research team - based in the Trinity Translational Medicine Institute which is collocated on the St. James's Hospital campus with the National TB Centre - are dedicated to defining how human immune responses to TB can be boosted to help kill off the bacteria. This will enable us to design immune boosting therapies that can be given alongside antibiotics to help people with TB fight off drug resistant infections.” 

What is the next step for this research?

The team plan to see if the IFN-γ training helps macrophages kill other pathogens like viruses or fungi. Another important step forward would be to recruit patients with tuberculosis disease or MRSA infections and see if we can train their macrophages ex vivo to better kill bacteria.

Funding: This work was funded by the Health Research Board (HRB) and the Royal City of Dublin Hospital Trust.

Read: You can read the full script: IFN-γ-induced trained immunity enhances killing of priority pathogens in healthy and genetically vulnerable individuals in the Journal of Clinical Investigation Insights at this link: https://insight.jci.org/articles/view/195866/pdf .

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