{"id":3353,"date":"2015-02-06T13:00:22","date_gmt":"2015-02-06T12:00:22","guid":{"rendered":"http:\/\/news.embl.de\/?p=3353"},"modified":"2024-11-29T16:54:49","modified_gmt":"2024-11-29T15:54:49","slug":"1502_anemia","status":"publish","type":"post","link":"https:\/\/www.embl.org\/news\/science\/1502_anemia\/","title":{"rendered":"The battle for iron"},"content":{"rendered":"\n

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\u2019s 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 could now take on new directions, as scientists in the Molecular Medicine Partnership Unit<\/a> of EMBL and Heidelberg University Clinic have found a hitherto unknown way through which mice starve pathogens of iron.<\/p>\n\n\n\n

Mammals keep iron out of reach of invading microbes by storing it in cells like macrophages \u2013 white blood cells which, among other things, normally \u2018recycle\u2019 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 Heidelberg and Martina Muckenthaler<\/a> 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.<\/p>\n\n\n\n

\"In
In response to infection, mice lock up iron (purple) in their macrophages (middle, right). IMAGE: Guida et al. Blood 2015<\/a><\/figcaption><\/figure><\/div>\n\n\n\n

\u201cUntil now, the main approach to develop treatments for anaemia of chronic disease was to look for anti-hepcidin therapies,\u201d says Hentze. \u201cOur findings provide an alternative approach, which is especially relevant because not all patients with anaemia of chronic disease have increased hepcidin levels.\u201d<\/p>\n\n\n\n

Why do these cells have two ways of decreasing ferroportin levels? \u201cIt 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\u2019re protected against: the hepcidin response might be triggered by some pathogens, and the TLR2\/TLR6 response could be activated by others,\u201d says Muckenthaler, \u201cor it could be that this TLR2\/TLR6 response we found is a first line of defense, and then the hepcidin response \u2018kicks in\u2019 later.\u201d<\/p>\n\n\n\n

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\u2019s anaemia is caused by problems in his or her TLR2\/TLR6 response.<\/p>\n\n\n\n

How it all came about<\/h4>\n\n\n\n

Matthias Hentze discusses how the team discovered this novel iron-sequestering strategy thanks to a screen developed with EMBL alumnus Michael Boutros<\/a>, now at the German Cancer Research Centre.<\/p>\n\n\n\n