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 Do microplastics harbour additional risks by colonization with harmful bacteria?
05.04.2018 | Leibniz-Institut für Ostseeforschung Warnemünde

nachricht Rutgers-led innovation could spur faster, cheaper, nano-based manufacturing
14.02.2018 | Rutgers University

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: Writing and deleting magnets with lasers

Study published in the journal ACS Applied Materials & Interfaces is the outcome of an international effort that included teams from Dresden and Berlin in Germany, and the US.

Scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) together with colleagues from the Helmholtz-Zentrum Berlin (HZB) and the University of Virginia...

Im Focus: Gamma-ray flashes from plasma filaments

Novel highly efficient and brilliant gamma-ray source: Based on model calculations, physicists of the Max PIanck Institute for Nuclear Physics in Heidelberg propose a novel method for an efficient high-brilliance gamma-ray source. A giant collimated gamma-ray pulse is generated from the interaction of a dense ultra-relativistic electron beam with a thin solid conductor. Energetic gamma-rays are copiously produced as the electron beam splits into filaments while propagating across the conductor. The resulting gamma-ray energy and flux enable novel experiments in nuclear and fundamental physics.

The typical wavelength of light interacting with an object of the microcosm scales with the size of this object. For atoms, this ranges from visible light to...

Im Focus: Basel researchers succeed in cultivating cartilage from stem cells

Stable joint cartilage can be produced from adult stem cells originating from bone marrow. This is made possible by inducing specific molecular processes occurring during embryonic cartilage formation, as researchers from the University and University Hospital of Basel report in the scientific journal PNAS.

Certain mesenchymal stem/stromal cells from the bone marrow of adults are considered extremely promising for skeletal tissue regeneration. These adult stem...

Im Focus: Like a wedge in a hinge

Researchers lay groundwork to tailor drugs for new targets in cancer therapy

In the fight against cancer, scientists are developing new drugs to hit tumor cells at so far unused weak points. Such a “sore spot” is the protein complex...

Im Focus: The Future of Ultrafast Solid-State Physics

In an article that appears in the journal “Review of Modern Physics”, researchers at the Laboratory for Attosecond Physics (LAP) assess the current state of the field of ultrafast physics and consider its implications for future technologies.

Physicists can now control light in both time and space with hitherto unimagined precision. This is particularly true for the ability to generate ultrashort...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

IWOLIA: A conference bringing together German Industrie 4.0 and French Industrie du Futur

09.04.2018 | Event News

 
Latest News

Diamond-like carbon is formed differently to what was believed -- machine learning enables development of new model

19.04.2018 | Materials Sciences

Electromagnetic wizardry: Wireless power transfer enhanced by backward signal

19.04.2018 | Physics and Astronomy

Ultrafast electron oscillation and dephasing monitored by attosecond light source

19.04.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>