Unearthing immune responses to common drugs

Drug immune complexes

Australian researchers, including a team from Monash University, are a step closer to understanding immune sensitivities to well-known, and commonly prescribed, medications.

Many drugs are successfully used to treat diseases, but can also have harmful side effects. While it has been known that some drugs can unpredictably impact on the functioning of the immune system, our understanding of this process has been unclear.

The team investigated what drugs might activate a specialised type of immune cell, the MAIT cell (Mucosal associated invariant T cell). They found that some drugs prevented the MAIT cells from detecting infections (their main role in our immune system), while other drugs activated the immune system, which may be undesirable.

The results, published in Nature Immunology on 7 February 2017, may lead to a much better understanding of, and an explanation for, immune reactions by some people to certain kinds of drugs. The findings may also offer a way to control the actions of MAIT cells in certain illnesses for more positive patient outcomes.

The multidisciplinary team of researchers are part of the ARC Centre of Excellence in Advanced Molecular Imaging, and stem from Monash University, The University of Melbourne and The University of Queensland. Access to national research infrastructure, including the Australian Synchrotron, was instrumental to the success of this Australian research team.

Dr Andrew Keller from Monash University’s Biomedicine Discovery Institute said that T cells are an integral part of the body’s immune system:

“They protect the body by ‘checking’ other cells for signs of infection and activating the immune system when they detect an invader,” Dr Keller said.

“This arrangement is dependent on both the T cells knowing what they’re looking for, and the other cells in the body giving them useful information.”

PhD student Weijun Xu from The University of Queensland’s Institute for Molecular Bioscience used computer modelling to predict chemical structures, drugs and drug-like molecules that might impact on MAIT cell function. Such small compounds included salicylates, non-steroidal anti-inflammatory drugs like diclofenac, and drug metabolites.

University of Melbourne Dr Sidonia Eckle from the Peter Doherty Institute for Infection and Immunity said the implications point to possible links between known drug hypersensitivities and MAIT cells.

“A greater understanding of the interaction between MAIT cells and other host cells will hopefully allow us to better predict and avoid therapeutics that influence and cause harm,” Dr Eckle said.

“It also offers the tantalising prospect of future therapies that manipulate MAIT cell behaviour, for example, by enhancing or suppressing immune responses to achieve beneficial clinical outcome.”

Ends

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.

About the Monash Biomedicine Discovery Institute

Committed to making the discoveries that will relieve the future burden of disease, the newly established Monash Biomedicine Discovery Institute at Monash University brings together more than 120 internationally-renowned research teams. Our researchers are supported by world-class technology and infrastructure, and partner with industry, clinicians and researchers internationally to enhance lives through discovery.