According to the World Health Organisation, tuberculosis (TB) is the world’s most fatal infectious disease. Each year it kills 1.5 million people and the growing number of drug-resistant cases means that new treatments are desperately needed.
Researchers at Trinity College Dublin’s School of Medicine, led by Clinical Research Fellow Dr Laura Gleeson, have been looking to respond to this need and, as their most recent findings show, they are obtaining promising results.
Their research, just published in the Journal of Immunology, uncovered a vital role for immune-metabolism in the host response (the reaction of a living system to the presence of a material). They found that important lung immune cells change the way cells metabolise sugar when they encounter the bacterium that causes TB. This is a metabolic change that is vital if cells are to produce the infection-fighting protein known as interleukin-1beta, which can ultimately kill the bug.
Their findings pave the way for the development of host-directed therapies that could be used to strengthen the immune response to TB. This would enhance the outcome of current treatments, and could be particularly useful for targeting drug-resistant strains.
“It’s very exciting,” says Dr Gleeson, “there are many metabolically-targeted drugs that are already licensed for clinical use for other diseases, so there are a lot of different possible agents that can now be investigated, and hopefully translated into improved TB treatments.”
However, she recognises that there is more work to be done: “We’ve discovered that this metabolic shift is extremely important in the early immune defence… What we need to do next is identify agents that enhance this metabolic shift to boost the body’s defence.”
Professor Joe Keane, a colleague of Dr Gleeson, added: “This is a game changer when it comes to new approaches to fighting TB. Instead of using antibiotics, which we have pretty much run out of, this discovery opens the door to use a new immune-therapy approach to improve existing treatments. There is a range of pre-existing drugs, which we know to be safe, and that can change how our immune system operates. Hence, if we can re-purpose some of these drugs to change metabolism, it may help our immune system fight TB, and because this is not an antibiotic approach, TB cannot go on to develop resistance to this form of attack.”
Dr Gleeson’s work is funded through a Health Professional Fellowship from the Health Research Board and through the Royal City of Dublin Hospital Trust. She relies heavily on patients attending St James’s Hospital for bronchoscopy, who generously allow small lung tissue samples to be used for research.