Lipocalin 2 mediates an innate immune response to bacterial infection by sequestrating iron

Although iron is required to sustain life, its free concentration and metabolism have to be tightly regulated 1 . This is achieved through a variety of iron-binding proteins including transferrin and ferritin 2 . During infection, bacteria acquire much of their iron from the host by synthesizing siderophores that scavenge iron and transport it into the pathogen 3 , 4 . We recently demonstrated that enterochelin, a bacterial catecholate siderophore, binds to the host protein lipocalin 2 (ref. 5 ). Here, we show that this event is pivotal in the innate immune response to bacterial infection. Upon encountering invading bacteria the Toll-like receptors on immune cells stimulate the transcription, translation and secretion of lipocalin 2; secreted lipocalin 2 then limits bacterial growth by sequestrating the iron-laden siderophore. Our finding represents a new component of the innate immune system and the acute phase response to infection.