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.
You can learn a lot about people if you mess with their minds. Here are four infamous experiments in which psychologists gave in to unethical temptations
The number of people without enough to eat has fallen rapidly over the past 25 years, but sub-Saharan Africa and parts of Asia are still struggling
New research raises serious questions about how artificial sweeteners might affect our bodies, but let's keep our cool and just do more research
Do you want to be a lab rat? That's what teenagers are doing when they smoke marijuana, the state of Colorado says. But since hard evidence of marijuana's harms is scanty, it may be a tough sell.
Caitlin Doughty has been cutting pacemakers out of corpses, grinding human bones by hand, and loading bodies into cremation chambers for seven years. But the 30-year-old mortician doesn't want to keep all the fun to herself: She thinks the rest of us should get to have a little more face time with the deceased.
A trial of an experimental vaccine against the Ebola virus is to begin in Oxford.
A simple urine test for the virus that causes cervical cancer could offer a less invasive and more acceptable alternative to the conventional cervical smear test, researchers said on Tuesday.
President Barack Obama and U.S. Senate commit to help West Africa wallop the virus
Many airlines don't want to have their crews overnight in an Ebola area or send them to a place where they can't get adequate health care if something goes wrong.
“Sic semper tyrannis,” Brutus supposedly yelled as he helped assassinate Julius Caesar: Thus always to tyrants. John Wilkes Booth exclaimed the same to the panicked crowd in Ford’s Theater after he shot Lincoln. And in dark underground burrows in east Africa, I’m willing to bet the homely yet somehow charming naked mole rat is yelling