One allows the immune system to work normally the other sends it to over drive.

Researchers have shown that there are two variants of Mal, a protein that alerts the immune system to respond against invading bacteria like malaria and tuberculosis. The combination of these variants determines how the immune system responds. Of the two variants, one allows the immune system to work normally, the other results in too strong a stimulation.

A person will carry a combination of two copies of the protein. “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,” explains Adrian Hill, Ph.D., from the Wellcome Trust Centre for Human Genetics, University of Oxford, U.K.. “Similarly, if you have two copies of the less active form, the body does not fight the infection and you get the disease.”

The scientists found that having the overactive Mal implied a four times greater risk of severe malaria in some populations.

“We hope that a drug that modulates the balance of Mal variants might prevent disease in those who are at greater risk,” says Luke O’Neill, who discovered the protein, from Trinity College Dublin, Ireland.

The researchers also believe that the findings may provide insight into how dysfunctional immune systems can lead to noninfectious diseases, specifically autoimmune diseases, such as type 1 diabetes and rheumatoid arthritis.

The results of the study are published in the April edition of Nature Genetics.

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