Battle for Iron: Control of Iron Levels Very Important in Defense Against Pathogens

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 anemia if the iron-starved state is sustained for too long, a common problem in chronically ill patients. The search for therapies against this anemia of chronic disease (ACD) could take on new directions thanks to a recent study published online on February 6, 2015 in Blood. In it, scientists in the Molecular Medicine Partnership Unit, a joint venture of the European Molecular Biology Laboratory (EMBL) and the 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 that this decrease in ferroportin could be achieved by increasing levels of hepcidin, a hormone which regulates iron levels. But Claudia Guida, a Ph.D. student in the group jointly led by Dr. Matthias Hentze at EMBL and Dr. Martina Muckenthaler at Heidelberg University Clinic, found that ferroportin can be dialed down independently of hepcidin, by triggering responses from TLR2 and TLR6, two molecules our immune system uses to detect bacterial components.
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