New mechanism that confers tolerance to malaria now revealed
Malaria is a life-threatening condition that exposes approximately half of the world's population to the risk of developing a severe and often lethal form of disease. In a study published in the latest issue of the journal Cell Host & Microbe*, Miguel Soares and his team at Instituto Gulbenkian de Ci-ncia (IGC), Portugal, discovered that the development of severe forms of malaria can be prevented by a simple mechanism that controls the accumulation of iron in tissues of the infected host. They found that expression of a gene that neutralizes iron inside cells, named H Ferritin, reduces oxidative stress preventing tissue damage and death of the infected host. This protective mechanism provides a new therapeutic strategy against malaria.
Malaria is the disease caused by infection with the parasite Plasmodium through the bites of infected mosquitoes. Infected individuals activate a series of defence mechanisms that aim at eliminating the parasite. However, this is not totally efficient in terms of avoiding severe forms of the disease and eventually death. There is another defence strategy that provides disease tolerance to malaria, reducing disease severity without targeting the parasite, as recently highlighted by Miguel Soares and collaborators in the journal Science**. The study now published in the journal Cell Host & Microbe* shows that this defence strategy acts via the regulation of iron metabolism in the infected host.
It was known that restricting iron availability to pathogens can reduce their virulence, that is, their capacity to cause disease. However, this defence strategy has a price, namely the accumulation of toxic iron in tissues and organs of the infected host. This can lead to tissue damage, enhancing rather than preventing disease severity. In the experimental work now conducted Raffaella Gozzelino, a senior researcher in Miguel Soares' laboratory, demonstrates that the infected host overcomes this problem by inducing the expression of H-Ferritin, which detoxifies iron. The protective effect of H-Ferritin prevents the development of severe and often lethal forms of malaria in mice.