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Australian and Irish Scientists identify triggers for our immune sentries

info Our guts, lungs and mouths are lined with specialised immune T cells which act as lookouts against invading bacteria and fungi. However, until now it was not known what triggers these cells to defend our bodies against infection.

Now researchers at the universities of Melbourne, Monash, Queensland and Cork have identified the precise biochemical key that activates these immune cells.

The new research, just published in Nature, provides the starting point to understanding our first line of defence against infection, 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 novel protective vaccines.

The researchers determined that these immune cells, known as mucosal-associated invariant T cells (MAITs), detect reactive intermediates in the synthesis of vitamin B2 (riboflavin) that is made by many invasive bacteria and fungi, but not by humans.

The latest discovery narrows the trigger down to a small group of compounds produced by specific bacteria and fungi, which may be associated with several diseases. The significance of this finding is in the fact that humans and other mammals use, but do not make, riboflavin; only bacteria and fungi do. This means that only bacteria and fungi are associated with riboflavin precursors of the type which send our MAITs into action. That makes our MAITs a useful guard against infection in our gut, mouth and lungs. And it means the diseases and microbes targeted by our MAITs can now be traced.

‘It has been an absolute privilege to be part of this international collaborative research team and to contribute our expertise on vitamin B2 biosynthesis by a bacterium that is normally used for cheese production. The fascinating discovery that an intermediate of bacterial vitamin biosynthesis is recognized by our immune system revealed the existence of a novel and highly sophisticated monitoring system for microbial invaders’ said Professor Douwe van Sinderen, who contributed to the research together with Dr Jennifer Mahony, at the Alimentary Pharmabiotic Centre and School of Microbiology, University College Cork.

Full Reference: T-cell activation by transitory neo-antigens derived from distinct microbial pathways

Alexandra J. Corbett, Sidonia B. G. Eckle, Richard W. Birkinshaw, Ligong Liu, Onisha Patel, Jennifer Mahony, Zhenjun Chen, Rangsima Reantragoon, Bronwyn Meehan, Hanwei Cao, Nicholas A. Williamson, Richard A. Strugnell, Douwe Van Sinderen, Jeffrey Y. W. Mak, David P. Fairlie, Lars Kjer-Nielsen, Jamie Rossjohn & James McCluskey

  • Photo (l-r) Jennifer Mahony and Douwe Van Sinderen

    14 April 2014