How our immune system targets tuberculosis

Every 18 seconds someone dies from tuberculosis - it is the world’s most deadly infectious disease.

Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), has infected more than one-third of the human population with an annual death toll of approximately 1.5 million people.

For the first time, an international team of scientists from Monash and Harvard Universities have seen how, at a molecular level, the human immune system recognises TB infected cells and initiates an immune response. Their findings, published in Nature Communications, are the first step toward developing new diagnostic tools and novel immunotherapies.

Lead author Professor Jamie Rossjohn from the Monash Biomedicine Discovery Institute said one of the main reasons for our current lack of knowledge was the complexity of the bacterium itself. Working with Professor Branch Moody’s team at Harvard, they have begun to gain key insight into how the immune system can recognise this bacterium.

Crucial to the success of M. tuberculosis as a pathogen is its highly unusual cell wall that not only serves as a barrier against therapeutic attack, but also modulates the host immune system. Conversely, its cell wall may also be the “Achilles’ heel” of mycobacteria as it is essential for the growth and survival of these organisms. This unique cell wall is comprised of multiple layers that form a rich waxy barrier, and many of these lipid — also known as fatty acids — components represent potential targets for T-cell surveillance.

Specifically, using the Australian Synchrotron, the team of scientists have shown how the immune system recognises components of the waxy barrier from the M. tuberculosis cell wall.

“With so many people dying from TB every year, any improvements in diagnosis, therapeutic design and vaccination will have major impacts,” Professor Moody says.

“Our research is focussed on gaining a basic mechanistic understanding of an important biomedical question. And may ultimately provide a platform for designing novel therapeutics for TB and treat this devastating disease,” Professor Rossjohn concludes.

Professor Jamie Rossjohn is a Chief Investigator at the Australian Research Council Centre of Excellence in Advanced Molecular Imaging.

About the Australian Research Council Centre of Excellence in Advanced Molecular Imaging

The $39 million ARC-funded Imaging CoE develops and uses innovative imaging technologies to visualise the molecular interactions that underpin the immune system. Featuring an internationally renowned team of lead scientists across five major Australian Universities and academic and commercial partners globally, the Centre uses a truly multi scale and programmatic approach to imaging to deliver maximum impact.

The Imaging CoE is headquartered at Monash University with four collaborating organisations – La Trobe University, the University of Melbourne, University of New South Wales and the University of Queensland.