Professor Luke O'Neill from Trinity College Dublin, Ireland, identified the protein in 2001. The protein, known as Mal, alerts the immune system to respond against invading bacteria. Now, Professor Adrian Hill from the Wellcome Trust Centre for Human Genetics, University of Oxford, UK, has shown that there are two variants of Mal in humans and that the combination of these variants determines how the immune system responds.
The results of the study, funded by the Wellcome Trust, Science Foundation Ireland, Irish Health Research Board and the Agency for Science, Technology and Research, Singapore, are published in the April edition of Nature Genetics this week.
"Mal is in effect an alarm system for the immune system," explains Professor O'Neill. "When the body is infected with the malaria parasite or other germs, a set of sensors called 'toll-like receptors' (TLRs) lock onto the intruder. TLRs relay the detection via Mal, which wakes up the immune system to mobilise and defend us."
However, working with patients in Kenya, the Gambia, Vietnam and the UK, Professor Hill and his team showed that there are two common variants of the protein, one which allows the immune system to work normally, the other resulting in too strong a stimulation. A person will carry a combination of two copies of the protein, one from the mother and one from the father.
"If you have the overactive type, you are twice as likely to succumb to infection because your immune system goes into overdrive, often leading to severe forms of the disease, in a manner akin to ‘friendly fire’," explains Professor Hill, a Wellcome Trust Principal Research Fellow. "Similarly, if you have two copies of the less active form, the body does not fight the infection and you get the disease. The optimum situation is to have one copy of each variant, giving a balanced system, sufficient to mount a response, but not overly activating."
The researchers found that having the overactive Mal doubled the risk of disease, with a four times greater risk of severe malaria in some populations. Malaria and TB account for over five million deaths per year in the developing world, particularly amongst children.
"We hope that a drug that modulates the balance of Mal variants might prevent disease in those who are at greater risk," says Professor O'Neill. "Our next step is to work towards developing such drugs."
The research has been welcomed by Dr Mark Walport, Director of the Wellcome Trust, which funds research into diseases of the developing world such as malaria and TB, mainly through its major overseas programmes.
"Malaria and TB present a major challenge to the health of people in the developing world," says Dr Walport. "Particularly given the recent rise in the number of cases of drug-resistant strains, it is essential that we understand how the immune system responds to infection if we are to develop novel treatments."
The researchers also believe that the findings may provide a valuable insight into how dysfunctional immune systems can lead to non-infectious diseases, specifically autoimmune diseases such as type 1 diabetes and rheumatoid arthritis.
Craig Brierley | alfa
Maelstroms in the heart
22.02.2018 | Max-Planck-Institut für Dynamik und Selbstorganisation
Decoding the structure of the huntingtin protein
22.02.2018 | Max-Planck-Institut für Biochemie
Quantum computers may one day solve algorithmic problems which even the biggest supercomputers today can’t manage. But how do you test a quantum computer to...
For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.
In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...
Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale
Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...
For photographers and scientists, lenses are lifesavers. They reflect and refract light, making possible the imaging systems that drive discovery through the microscope and preserve history through cameras.
But today's glass-based lenses are bulky and resist miniaturization. Next-generation technologies, such as ultrathin cameras or tiny microscopes, require...
Scientists from the University of Zurich have succeeded for the first time in tracking individual stem cells and their neuronal progeny over months within the intact adult brain. This study sheds light on how new neurons are produced throughout life.
The generation of new nerve cells was once thought to taper off at the end of embryonic development. However, recent research has shown that the adult brain...
15.02.2018 | Event News
13.02.2018 | Event News
12.02.2018 | Event News
22.02.2018 | Life Sciences
22.02.2018 | Information Technology
22.02.2018 | Health and Medicine