An international team of researchers has identified a key protein involved in the immune system's response to malaria, tuberculosis (TB) and a number of other infectious diseases. The insights suggest possible new therapies to tackle these major global diseases.
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."