The precise biochemical key that wakes up the body's immune cells and sends them into action against invading bacteria and fungi has been identified by an international team of scientists.
The patented work, published in Nature, provides the starting point to understanding our first line of defence, and what happens when it goes wrong. It will lead to new ways of diagnosing and treating inflammatory bowel disease, peptic ulcers and even TB. It could also lead to new protective vaccines.
The discovery, the result of an international collaboration between Monash University and the Universities of Melbourne, Queensland and Cork, builds on work by Australian researchers last year who proved that a group of immune cells called MAITs, which line the gut, lungs and mouth, act as defenders against bacteria. Making up to 10 per cent of T-cells, which are essential to the immune system, mucosal-associated invariant T (MAITs) initiate the immune system's action against foreign invaders when they are exposed to vitamin B2, which is made by bacteria and fungi.
Professor Jamie Rossjohn from the School of Biomedical Sciences at Monash University said that access to major facilities in Melbourne played a critical role in the research.
"To get from the first observation to today's discovery required not just smart people but access to Melbourne's Bio21 Institute platforms, dozens of visits to the Australian Synchrotron, and a global research network including our Irish colleagues who provided access to mutant bacterial strains. All that coming together allowed us to beat our international competitors and secure the patent," Professor Rossjohn said.
Professor James McCluskey, Deputy Vice-Chancellor (Research) from The University of Melbourne said little was known about the role of MAITs, beyond the fact that they had an association with bacteria. This latest research narrows down the biochemical trigger for MAIT cells to a particular group of compounds. The reaction is only possible in certain bacteria and fungi, which means the diseases and microbes targeted by the body's MAITs can now be traced.
"We want to unravel the complex molecular interactions that define how we fight disease. This remarkable research collaboration shows us how to do it," Professor McCluskey said.
The research proves that humans and other mammals use but do not make riboflavin; only bacteria and fungi do, which means that MAITs are a useful guard against infection in the gut, mouth and lungs.
Researcher Dr Alexandra Corbett, from The University of Melbourne said the discovery was significant. "We have unlocked a secret that will enable our team to investigate the role that MAIT cells play in health and disease, which is exciting. However, there are major international laboratories with whom we have to compete."
Professor David Fairlie of the Institute for Molecular Bioscience at the University of Queensland said the finding may be a valuable clue to fight disease and assist with new drug developments.
"MAIT cells are a discovery so recent that they have not even made it into the textbooks. Most doctors know nothing about them. Yet they constitute about one cell in 10 of the body's T-cells and half of all the T-cells in the liver," Professor McCluskey said.
The work is also an early win for the recently announced ARC Centre of Excellence in Advanced Molecular Imaging. The Centre develops new imaging methods to visualise atomic, molecular and cellular details of how immune proteins interact and affect immune responses.