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Copycat fungus deceives immune system and deactivates body's response to infection

March 28, 2019

Fungus can imitate signals from our immune system and prevent our body from responding to infection, new research from the University of Sheffield has found.

Life-threatening fungal infection is a major killer of people with immune system problems such as blood cancers, HIV infection or following organ transplant.

The new study focused on one of the most dangerous infections for people with HIV/AIDS - Cryptococcus neoformans - which causes hundreds of thousands of deaths worldwide every year.

Fungi are known to make molecules similar to those of our own immune system, but why fungi make these molecules and what their function is has been a longstanding mystery.

Now, scientists from the University of Sheffield have identified how specific immune signals called prostaglandins, made by fungi, are able to disarm immune cells.

The team, led by Dr Simon Johnston from the University's Department of Infection, Immunity and Cardiovascular Disease, found that fungi which are not able to make these signals were less able to grow during infection.

Dr Johnston, Senior Research Fellow in Infectious Disease, said: "We've discovered that these immune signals - fungal prostaglandins - deactivate immune cells, preventing them from destroying the infection.

"We found the fungus was activating a normal immune pathway that prevents overstimulation of the immune system, but is essential in stopping infections.

"Opportunistic infections like Cryptococcus - which normally pose no threat, but are potentially life-threatening in those with weakened immune systems - are an increasing problem and are often very difficult to treat.

"Understanding how opportunistic infections cause disease is vital in order to develop new and more effective treatments, especially with the increase in antibiotic resistant infections."

Dr Johnston added: "We are now working to find other ways these fungal molecules are affecting immune cells and how the immune cells are deactivated.

"The same deactivation of immune cells is seen in other diseases such as cancer. Our findings mean that we now have a new approach to solving this problem and will help the development of new treatments."

The study, published today (28 March 2019) in the journal PLoS Pathogens (DOI : http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1007597) was funded by the Medical Research Council (MRC) and British Infection Association.

Dr Anna Kinsey, programme manager for viral and fungal infections at the MRC, said: "The MRC's investment in fungal research, and in future leaders in this field, is important.

"Current anti-fungal therapies are poorly tolerated and toxic and, significantly, resistance to these agents is increasing. As such, there is an urgent need for new treatments, which first requires a better understanding of the interaction of the fungal pathogen with the body's immune system.

This research provides a window into how C. neoformans manipulates the immune system to promote its own growth and increase infection."
-end-
The University of Sheffield's Department of Infection, Immunity and Cardiovascular Disease is a world-leading centre pioneering discoveries which help to fight disease and inform inspirational teaching.

For more information please visit: https://www.sheffield.ac.uk/iicd/index

For further information please contact: Amy Huxtable, Media Relations Officer, University of Sheffield, 0114 222 9859, a.l.huxtable@sheffield.ac.uk

Notes to editors

The University of Sheffield

With almost 29,000 of the brightest students from over 140 countries, learning alongside over 1,200 of the best academics from across the globe, the University of Sheffield is one of the world's leading universities.

A member of the UK's prestigious Russell Group of leading research-led institutions, Sheffield offers world-class teaching and research excellence across a wide range of disciplines.

Unified by the power of discovery and understanding, staff and students at the university are committed to finding new ways to transform the world we live in.

Sheffield is the only university to feature in The Sunday Times 100 Best Not-For-Profit Organisations to Work For 2018 and for the last eight years has been ranked in the top five UK universities for Student Satisfaction by Times Higher Education.

Sheffield has six Nobel Prize winners among former staff and students and its alumni go on to hold positions of great responsibility and influence all over the world, making significant contributions in their chosen fields.

Global research partners and clients include Boeing, Rolls-Royce, Unilever, AstraZeneca, Glaxo SmithKline, Siemens and Airbus, as well as many UK and overseas government agencies and charitable foundations.

The Medical Research Council (MRC)

The Medical Research Council is at the forefront of scientific discovery to improve human health. Founded in 1913 to tackle tuberculosis, the MRC now invests taxpayers' money in some of the best medical research in the world across every area of health. Thirty-three MRC-funded researchers have won Nobel prizes in a wide range of disciplines, and MRC scientists have been behind such diverse discoveries as vitamins, the structure of DNA and the link between smoking and cancer, as well as achievements such as pioneering the use of randomised controlled trials, the invention of MRI scanning, and the development of a group of antibodies used in the making of some of the most successful drugs ever developed. Today, MRC-funded scientists tackle some of the greatest health problems facing humanity in the 21st century, from the rising tide of chronic diseases associated with ageing to the threats posed by rapidly mutating micro-organisms. The Medical Research Council is part of UK Research and Innovation. https://mrc.ukri.org/

University of Sheffield

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