Researchers uncover new insights into how mosquitoes' immune systems fight off deadly parasites<me> - News Release</em>

Imperial College London news release

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Thursday 5 March 2009

The means by which most deadly malaria parasites are detected and killed by the mosquitoes that carry them is revealed for the first time in research published today (5 March) in Science Express. The discovery could help researchers find a way to block transmission of the disease from mosquitoes to humans.

Mosquitoes become infected with malaria when they feed on the blood of an infected person. Young malaria parasites then grow and develop inside the mosquito for two weeks. New human infections occur when these parasites are 'injected' with the insect's saliva during the mosquito's next blood meal.

However, most of the malaria parasites are killed by the mosquito's immune system as soon as they enter the insect's bloodstream, with only one or two slipping through the net and going on to divide, multiply, and infect people.

A malaria parasite (red) has invaded a mosquito cell, which is dying as a result.

The new study shows exactly how the mosquito's immune system kicks in to kill 80 – 90 percent of the parasites. The researchers discovered that the parasites are detected by a pair of proteins called LRIM1 and APL1C which belong to the mosquito's infection surveillance system. These two 'intruder detection' proteins then activate a third protein in the mosquito's blood called TEP1, which seeks out the parasitic invader, binds to its surface and orchestrates its destruction by punching holes in its cell membrane.

The Imperial College London team behind the new discovery say this knowledge could be used to develop new genetic or chemical techniques to improve on the mosquito's natural detection success rate, so that 100 percent of the parasites can be killed inside the mosquito, preventing transmission of the disease from insects to people.

Dr George Christophides from Imperial's Department of Life Sciences comments: "Mosquitoes are known as the 'bad guys' that spread malaria, but these insects are unwilling carriers of the disease, whose immune systems try to fight it, just like ours do. Now that we know exactly how their immune system attacks malaria parasites, we need to work out how a small number of parasites manage to evade detection by this system. Only a few manage to get past the mosquito's defences, but that's all that's needed for the disease to be transmitted to humans.

"If we can figure out how some parasites manage to sneak through undetected, hopefully we can find a way to bolster the mosquito's defences to catch them all."

The research, which was funded by the Wellcome Trust, the Biotechnology and Biological Sciences Research Council (BBSRC), and the National Institute of Allergy and Infectious Diseases of the U.S. National Institutes of Health, was carried out in the laboratory using a model parasite which causes malaria in rodents.

Half the global population are at risk of contracting malaria and up to half a billion new infections are recorded every year. Between one and three million people die from malaria every year – the majority of fatalities are children living in sub-Saharan Africa.

Apart from malaria, mosquitoes also spread other serious infectious diseases such as dengue and yellow fever, filariasis and various encephalitides. Dr Christophides and his colleagues at Imperial also discovered that LRIM1 and APL1C belong to a family of infection detection proteins that appear to be specific to mosquitoes. The researchers believe that proteins in this family may play a role in defence against these other infections too, and are currently investigating how these proteins function during mosquito infection with dangerous human pathogens.

-Ends-

For more information please contact:
Danielle Reeves, Imperial College London press office
Tel: +44 (0)20 7594 2198
Out-of-hours duty press office: +44 (0)7803 886248
Email: Danielle.reeves@imperial.ac.uk

Notes to Editors:

1. 'Leucine-rich repeat protein complex activates mosquito complement in defense against Plasmodium parasites', Science Express, online publication Thursday 5 March 2009.

Michael Povelones, Robert M. Waterhouse, Fotis C. Kafatos & George K. Christophides.

Division of Cell and Molecular Biology, Department of Life Sciences, Imperial College London, Exhibition Road, London SW7 2AZ, United Kingdom

2. About Imperial College London

Consistently rated amongst the world's best universities, Imperial College London is a science-based institution with a reputation for excellence in teaching and research that attracts 13,000 students and 6,000 staff of the highest international quality.

Innovative research at the College explores the interface between science, medicine, engineering and business, delivering practical solutions that improve quality of life and the environment - underpinned by a dynamic enterprise culture.

Since its foundation in 1907, Imperial's contributions to society have included the discovery of penicillin, the development of holography and the foundations of fibre optics. This commitment to the application of research for the benefit of all continues today, with current focuses including interdisciplinary collaborations to improve health in the UK and globally, tackle climate change and develop clean and sustainable sources of energy.

Website: //www.imperial.ac.uk

3. About the Wellcome Trust

The Wellcome Trust is the largest charity in the UK. It funds innovative biomedical research, in the UK and internationally, spending over £600 million each year to support the brightest scientists with the best ideas. The Wellcome Trust supports public debate about biomedical research and its impact on health and wellbeing.

Website: http://www.wellcome.ac.uk

4. About the the Biotechnology and Biological Sciences Research Council

The Biotechnology and Biological Sciences Research Council (BBSRC) is the UK funding agency for research in the life sciences. Sponsored by Government, BBSRC annually invests around £420 million in a wide range of research that makes a significant contribution to the quality of life for UK citizens and supports a number of important industrial stakeholders including the agriculture, food, chemical, healthcare and pharmaceutical sectors. BBSRC carries out its mission by funding internationally competitive research, providing training in the biosciences, fostering opportunities for knowledge transfer and innovation and promoting interaction with the public and other stakeholders on issues of scientific interest in universities, centres and institutes.

The Babraham Institute, Institute for Animal Health, Institute of Food Research, John Innes Centre and Rothamsted Research are Institutes of BBSRC. The Institutes conduct long-term, mission-oriented research using specialist facilities. They have strong interactions with industry, Government departments and other end-users of their research.

For more information see: http://www.bbsrc.ac.uk

5. About the NIH

The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), conducts and supports research worldwide to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses, see: http://www.niaid.nih.gov

NIH includes 27 Institutes and Centers and is a component of the U. S. Department of Health and Human Services. It is the primary U.S. federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments and cures for both common and rare diseases.

Website: http://www.nih.gov