Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Tolerance to malaria by means of iron control

15.11.2012
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 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 Plasmodium in 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.

This research was carried out at the IGC in collaboration with researchers from the National Institutes of Health (NIH), USA, Fundação Oswaldo Cruz (FIOCRUZ), Brazil, Faculdade de Medicina da Universidade Federal da Bahia, Brazil, Ecole Polytechnique Federale de Lausanne (EPFL), Swiss Institute for Experimental Cancer Research (ISREC), Switzerland, and University of Brescia, Italy. This project was funded by Fundação para a Ciência e a Tecnologia (Portugal), the European Commission's Framework Programme 6, Financiadora de Estudos e Projetos/Fundo Nacional de Desenvolvimento Científico e Tecnológico Amazônia (Brazil), Conselho Nacional de Pesquisa e Tecnologia (Brasil), Conselho Nacional de Ciência e Tecnologia (CNPq) (Brazil) and NIH.

*Raffaella Gozzelino, Bruno Bezerril Andrade, Rasmus Larsen, Nivea F. Luz, Liviu Vanoaica, Elsa Seixas, António Coutinho, Sílvia Cardoso, Sofia Rebelo, Maura Poli, Manoel Barral-Neto, Deepak Darshan, Lukas C. Kühn and Miguel P. Soares. (2012) Metabolic Adaptation to Tissue Iron Overload Confers Tolerance to Malaria. Cell Host & Microbe 12: 693-704.

** Ruslan Medzhitov, David S. Schneider and Miguel P. Soares. (2012) Disease Tolerance as a Defense Strategy. Science 335: 936-941.

Ana Mena | EurekAlert!
Further information:
http://www.igc.gulbenkian.pt

More articles from Studies and Analyses:

nachricht Europe’s Demographic Future. Where the Regions Are Heading after a Decade of Crises
10.08.2017 | Berlin-Institut für Bevölkerung und Entwicklung

nachricht Scientists reveal source of human heartbeat in 3-D
07.08.2017 | University of Manchester

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

New bioimaging technique is fast and economical

21.08.2017 | Medical Engineering

Silk could improve sensitivity, flexibility of wearable body sensors

21.08.2017 | Materials Sciences

On the way to developing a new active ingredient against chronic infections

21.08.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>