The Mal protein modifies the immune response to Mycobacterium tuberculosis

Hardin MD

[NAIROBI] Researchers have identified a way that the immune system responds to malaria and tuberculosis infections, suggesting new therapies to tackle these and other diseases.

They found two variants of a key protein called Mal that alerts the body's immune system to the presence of invading bacteria. One variant allows the immune system to respond normally, whilst the other causes too strong a reaction.

The study, published in the April edition of Nature Genetics, shows that an imbalance in the two variants can make someone more vulnerable to disease.

A person carries two copies of the Mal protein, one from the mother and one from the father.

Possessing two copies of the less active variant means the body will not respond sufficiently to infection and will succumb to disease, while two copies of the highly active variant means the immune system goes into overdrive, leading to severe forms of the disease.

"Having both variants seems ideal, that is, one from each parent. That allows a medium signal to be transmitted, leading to the right magnitude of inflammatory response," lead researcher Adrian Hill of the UK-based Wellcome Trust Centre for Human Genetics told SciDev.Net.

The team say a drug could be developed to modulate the balance of Mal variants in people that are at higher risk of imbalance. "Our next step is to work towards developing such drugs," says Hill.

The researchers studied 6,106 individuals from Algeria, Gambia, Guinea Bissau, the Republic of Guinea, Kenya, the UK and Vietnam with pneumococcal disease, bacterial infection of the blood, malaria and tuberculosis.

"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" added Mark Walport, director of the Wellcome Trust.