Proteins responsible for controlling levels of iron in the body also play an important role in combatting infection, according to a study published today in Cell Host & Microbe.
Humans - along with all living organisms, including pathogens - need iron to survive: invading organisms try to highjack it from their hosts in order to thrive and multiply. Researchers at EMBL Heidelberg, and their colleagues, have now discovered that proteins responsible for helping the body maintain the correct levels of iron at a cellular level are also involved in helping to prevent this theft. These proteins form a system called IRP/IRE (iron regulatory protein/iron responsive element).
Fluorescence microscopy picture of bone marrow-derived macrophages: red: macrophage marker/ blue: DNA /green: ferritin. Compared to the few control cells present in this picture, IRP-null macrophages express abnormally high levels of ferritin (green), which constitutes a pool of iron Salmonella can exploit.
Credit: Bruno Galy/DKFZ
"The work we've been doing has uncovered a connection between two very important functions that are typically seen as separate: the body's innate immune system, and its iron metabolism," explains Matthias Hentze, co-author of the paper and Director of EMBL.
The team analysed how mice reacted to an infection by the Salmonella bacteria, depending on whether they had a functional IRP/IRE system or not. Mice lacking a functional IRP/IRE system from professional immune cells called macrophages did well as long as they were not infected, but when the Salmonella bacteria were introduced, they died. This showed that the iron regulatory system was crucial for the macrophages, the target-cells for this specific pathogen, to fight off the infection effectively.
"Withholding iron from an invading pathogen is an innate defence against infection," explains Bruno Galy, former Staff Scientist at EMBL-Heidelberg and currently group leader at the German Cancer Research Centre (DKFZ). "Our study reveals that the IRP/IRE system plays an important role in this defence."
The precise mechanisms through which the IRP/IRE system works in the macrophages will need further investigation, although the researchers have a number of theories.
One theory is that the IRP proteins help the macrophages produce a molecule called lipocalin 2, which is known to block bacteria from taking up iron from its host. Another idea is that the IRP/IRE system represses the expression of a protein called ferritin. Ferritin is present in cells as a kind of compartment to store iron until it is needed. Invading bacteria get access to these iron supplies and if the IRP proteins are not present, the cell will store much more iron than required - thus providing valuable nutrients for invaders.
The group now plan to carry out further investigations to find out if the IRP/IRE system is also important for other types of bacteria, and other types of infection, such as viruses or parasites. They also hope to discover if the IRP/IRE system has a role to play in other types of immune response, such as inflammation. This immune response is implicated in the progress of human diseases such as cancer or atherosclerosis so a better understanding of its mechanisms could have implications for research into new treatments.
The research was carried out in partnership with Guenter Weiss and colleagues at the Medical University of Innsbruck and Ferric Fang at the University of Washington.
Isabelle Kling | European Molecular Biology Laboratory
How molecules teeter in a laser field
18.01.2019 | Forschungsverbund Berlin
Discovery of enhanced bone growth could lead to new treatments for osteoporosis
18.01.2019 | University of California - Los Angeles
The scientific and political community alike stress the importance of German Antarctic research
Joint Press Release from the BMBF and AWI
The Antarctic is a frigid continent south of the Antarctic Circle, where researchers are the only inhabitants. Despite the hostile conditions, here the Alfred...
World first experiments on sensor that may revolutionise everything from medical devices to unmanned vehicles
The new sensor - capable of detecting vibrations of living cells - may revolutionise everything from medical devices to unmanned vehicles.
Dead and alive at the same time? Researchers at the Max Planck Institute of Quantum Optics have implemented Erwin Schrödinger’s paradoxical gedanken experiment employing an entangled atom-light state.
In 1935 Erwin Schrödinger formulated a thought experiment designed to capture the paradoxical nature of quantum physics. The crucial element of this gedanken...
Cellulose obtained from wood has amazing material properties. Empa researchers are now equipping the biodegradable material with additional functionalities to produce implants for cartilage diseases using 3D printing.
It all starts with an ear. Empa researcher Michael Hausmann removes the object shaped like a human ear from the 3D printer and explains:
The phenomenon of so-called superlubricity is known, but so far the explanation at the atomic level has been missing: for example, how does extremely low friction occur in bearings? Researchers from the Fraunhofer Institutes IWM and IWS jointly deciphered a universal mechanism of superlubricity for certain diamond-like carbon layers in combination with organic lubricants. Based on this knowledge, it is now possible to formulate design rules for supra lubricating layer-lubricant combinations. The results are presented in an article in Nature Communications, volume 10.
One of the most important prerequisites for sustainable and environmentally friendly mobility is minimizing friction. Research and industry have been dedicated...
16.01.2019 | Event News
14.01.2019 | Event News
12.12.2018 | Event News
18.01.2019 | Materials Sciences
18.01.2019 | Life Sciences
18.01.2019 | Health and Medicine