When we think of how we fight disease, the image of cells in our immune system fending off microbial invaders often comes to mind. Another strategy our bodies can employ is to cut off the enemy’s supply lines and effectively starve disease-causing microbes of the iron they need to function.
However, this tactic can backfire and cause anaemia if the iron-starved state is sustained for too long, a common problem in chronically ill patients. The search for therapies against this anaemia of chronic disease (ACD) could take on new directions thanks to a study published today in Blood.
In it, scientists in the Molecular Medicine Partnership Unit, a joint venture of the European Molecular Biology Laboratory (EMBL) and Heidelberg University Clinic, both in Heidelberg, Germany, have found a hitherto unknown way through which mice starve pathogens of iron.
Mammals keep iron out of reach of invading microbes by storing it in cells like macrophages – white blood cells which, among other things, normally ‘recycle’ the iron from red blood cells back into the bloodstream. When the body is under attack, macrophages respond by decreasing levels of their iron-exporter, ferroportin, thereby sequestering the iron.
Scientists knew this decrease in ferroportin could be achieved by increasing levels of hepcidin, a hormone which regulates iron levels. But Claudia Guida, a PhD student in the group jointly led by Matthias Hentze at EMBL and Martina Muckenthaler at Heidelberg University Clinic, found that ferroportin can be dialled down independently of hepcidin, by triggering responses from TLR2 and TLR6, two molecules our immune system uses to detect bacterial components.
“Until now, the main approach to develop treatments for anaemia of chronic disease was to look for anti-hepcidin therapies,” says Hentze. “Our findings provide an alternative approach, which is especially relevant because not all patients with anaemia of chronic disease have increased hepcidin levels.”
Why do these cells have two ways of decreasing ferroportin levels? “It could be that this is such an important response, that organisms have evolved a fail-safe, so that if one response fails, they have the other; or it could be a way of broadening the spectrum of what you’re protected against: the hepcidin response might be triggered by some pathogens, and the TLR2/TLR6 response could be activated by others,” says Muckenthaler, “or it could be that this TLR2/TLR6 response we found is a first line of defense, and then the hepcidin response ‘kicks in’ later.”
Hentze, Muckenthaler and colleagues are now investigating exactly what causes ferroportin levels to decrease when TLR2 and TLR6 are activated. As well as informing the search for therapies, this could one day help to develop tests to determine if a patient’s anaemia is caused by problems in his or her TLR2/TLR6 response.
Published online in Blood on 6 February 2015. DOI: 10.1182/blood-2014-08-595256.
For images and more information please visit: http://s.embl.org/EMBLpr060215
Policy regarding use
EMBL press and picture releases including photographs, graphics and videos are copyrighted by EMBL. They may be freely reprinted and distributed for non-commercial use via print, broadcast and electronic media, provided that proper attribution to authors, photographers and designers is made.
Sonia Furtado Neves
EMBL Press Officer & Deputy Head of Communications
Meyerhofstr. 1, 69117 Heidelberg, Germany
Tel.: +49 (0)6221 387 8263
Fax: +49 (0)6221 387 8525
Sonia Furtado Neves | European Molecular Biology Laboratory
Finnish research group discovers a new immune system regulator
23.02.2018 | University of Turku
Minimising risks of transplants
22.02.2018 | Friedrich-Alexander-Universität Erlangen-Nürnberg
A newly developed laser technology has enabled physicists in the Laboratory for Attosecond Physics (jointly run by LMU Munich and the Max Planck Institute of Quantum Optics) to generate attosecond bursts of high-energy photons of unprecedented intensity. This has made it possible to observe the interaction of multiple photons in a single such pulse with electrons in the inner orbital shell of an atom.
In order to observe the ultrafast electron motion in the inner shells of atoms with short light pulses, the pulses must not only be ultrashort, but very...
A group of researchers led by Andrea Cavalleri at the Max Planck Institute for Structure and Dynamics of Matter (MPSD) in Hamburg has demonstrated a new method enabling precise measurements of the interatomic forces that hold crystalline solids together. The paper Probing the Interatomic Potential of Solids by Strong-Field Nonlinear Phononics, published online in Nature, explains how a terahertz-frequency laser pulse can drive very large deformations of the crystal.
By measuring the highly unusual atomic trajectories under extreme electromagnetic transients, the MPSD group could reconstruct how rigid the atomic bonds are...
Quantum computers may one day solve algorithmic problems which even the biggest supercomputers today can’t manage. But how do you test a quantum computer to...
For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.
In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...
Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale
Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...
15.02.2018 | Event News
13.02.2018 | Event News
12.02.2018 | Event News
23.02.2018 | Physics and Astronomy
23.02.2018 | Health and Medicine
23.02.2018 | Physics and Astronomy