Innate Immune System and Iron Metabolism Work Together to Fight Off Pathogens; Functional IRP/IRE System Key to Denying Crucial Iron to Potential Invaders

Proteins responsible for controlling levels of iron in the body also play an important role in combatting infection, according to a study published online on July 16, 2015 in Cell Host & Microbe. The article is titled “Iron Regulatory Proteins Mediate Host Resistance to Salmonella Infection.” Humans, along with all living organisms, including pathogen, 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). “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 Dr. Matthias Hentze, co-author of the paper and Director of EMBL. The research team analyzed 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, the mice 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 defense against infection,“ explains Dr. Bruno Galy, former Staff Scientist at EMBL-Heidelberg and currently Group Leader at the German Cancer Research Centre (DKFZ).
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