New tool reveals how special immune cells fight bacteria

We all know that green leafy vegetables, seafood, meat, dairy, cereals and even mushrooms, almonds and vegemite are all healthy for us. One essential ingredients in them is vitamin B2 (riboflavin) — this is because vitamin B2 enriches our immune system.

But did you know that some bacteria in our bodies also make this vitamin?

Scientists from the Imaging CoE, based at the Universities of Queensland, Melbourne and Monash, recently learnt that when bacteria produce this vitamin, they leave behind a trail of chemical footprints that are invisible under microscopes and vanish in minutes. Two chemists at the University of Queensland’s Institute for Molecular Bioscience, who are postdocs on the Imaging CoE, Jeff Mak and Ligong Liu, have managed to make these chemicals in a test tube.

This reserach presents big step towards improving the way we study immune responses to bacterial infections.

T cells are immune cells that play a key role in our immune response. They are able to recognise early signs of infection and then trigger an immune reaction that destroys invading pathogens. While much is known about how the majority of T cells function, it is not quite clear how this process works in an important subset of T cells, called MAIT cells.

MAIT cells make up nearly half the T cells in the liver, and account for around 10 per cent of the T cells in blood. MAIT cells are also important to our immune response against many types of bacteria. Yet it isn’t clear why some bacterial infections are able to overwhelm MAIT cells to become persistent, potentially fatal infections. MAIT cells are also believed to play a role in a number of autoimmune diseases and may even play a role in cancer, but precisely how MAIT cells might contribute to these conditions is not well understood.

A major reason that MAIT cells are still something of a mystery is that they have been very hard to activate in the lab, because until recently no one knew exactly what part of the bacteria triggers their activation.

In 2014, Imaging CoE CI David Fairlie and his interstate collaborators identified a molecule produced by many bacteria that MAIT cells recognise and react to. Bacteria must produce their own vitamin B2 in order to survive and multiply. But vitamin B2 production is a step-by-step process. During one of these steps, bacteria make a molecule known as an ‘intermediate’, which is a not-quite-finished version of vitamin B2. This intermediate is then further modified to form the molecule that triggers MAIT cells.

Imaging CoE investigators based at the IMB, Dr Jeffrey Mak and Dr Ligong Liu, who worked with CI David Fairlie to identify this molecule, explain that this 2014 discovery provided immunology researchers around the world with a clue as to how MAIT cells function, but unfortunately the molecule was too unstable to use, breaking down extremely quickly in water.

Now, in a paper published overnight in the journal Nature Communications (DOI 10.1038/NCOMMS14599), the IMB research team has determined the right chemical conditions that enable this molecule to survive long enough to be isolated, stored, and then used in experiments.

“We found the sweet spot,” Dr Mak said. “It’s a fundamental discovery that will help us understand how our body fights bacteria.”

In collaboration with Imaging CoE researchers at the University of Melbourne and Monash University, Professor Fairlie and his team built a computer model to analyse how the molecule works. Then, they used that information to create a highly stable version of the molecule. This synthetic mimic is able to activate MAIT cells, meaning that immunology researchers can use this new, more durable molecule in a wider variety of experiments. This molecule may even eventually help the team to develop a drug capable of stimulating the immune system.

“By learning how to make these trace chemicals from bacteria, scientists around the world now have new tools to find traces of infection in our body and new clues to fight disease,” Dr Liu said.

Content by the Institute for Molecular Bioscience

The Institute for Molecular Bioscience is an outstanding research institute located at the University of Queensland, in Brisbane, Australia. The IMB’s mission is to decipher the information contained in the genes, proteins and molecules of humans, animals and plants.