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 Ciência (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.
The researchers also investigated if there is a correlation between the severity of malaria and the expression of ferritin in humans. Together with Bruno Bezerril Andrade (currently at the National Institute of Allergy and Infectious Diseases, NIH, USA), Nivea Luz and Manoel Barral-Netto (at Fundação Oswaldo Cruz and Faculdade de Medicina, Universidade Federal da Bahia, Brazil) they analyzed samples from individuals infected with Plasmodiumin Rondônia, a state in the north-western part of Brazil. Their results showed that, among the infected individuals, those with higher levels of ferritin presented reduced tissue damage. Together with the experimental data obtained in mice, these observations reveal that ferritin confers protection against malaria, without interfering directly with the parasite causing the disease, that is, that ferritin confers disease tolerance to malaria.
Miguel Soares says: 'Our work suggests that individuals that express lower levels of Ferritin and hence are not so efficient at sequestering toxic iron in their tissues might be at a higher risk of developing severe forms of malaria. Furthermore, our study also supports a theory that explains how protection against malaria, as well as other infectious diseases, can operate without targeting directly the causative agent of disease, namely Plasmodium. Instead, this defence strategy works by protecting cells, tissue and organs in the infected host from dysfunction, thus limiting the severity of disease.'
This study opens the way to new therapeutics that could confer tolerance to malaria.
Instituto Gulbenkian de Ciencia: http://www.igc.gulbenkian.pt
This press release was posted to serve as a topic for discussion. Please comment below. We try our best to only post press releases that are associated with peer reviewed scientific literature. Critical discussions of the research are appreciated. If you need help finding a link to the original article, please contact us on twitter or via e-mail.
Scientists develop test for three proteins which could give early warning of disease and help doctors distinguish symptoms from chronic pancreatitis
A series of experiments has produced incredible results by giving young blood to old mice. Now the findings are being tested on humans.
A probe inserted into a person's brain can alert intensive-care staff to a critical drop in energy supply, potentially saving the patient's life
Tests that detect changes in genes triggered by drugs could bolster the use of a biological passport – if athletics will spend more on research
The drug derived from the venom of cone snails must be injected into the spinal column to get beyond a patient's blood-brain barrier and bring relief. But scientists think they may have a workaround.
For some unknown reason, the insects that transmit sleeping sickness in sub-Saharan Africa are attracted to the color blue. So scientists think blue flytraps could help wipe out the disease for good.
Pharmacology can get a bad rap in the press. Professors George Davey Smith and David Nutt fight the case for statins and SSRIs.
People who spend time watching fish swim in aquarium tanks could improve their physical and mental wellbeing, a study shows.
The chytrid fungus has wiped out populations of amphibians around the world. A type of the fungus infects only salamanders, and researchers have identified vulnerable areas in North America.
NPR's Melissa Block speaks with the AP's Brazil bureau chief Brad Brooks about the investigation, which found high levels of dangerous viruses in water venues for the 2016 Summer Olympics.