title: Lipocalin 2 mediates an innate immune response to bacterial infection by sequestrating iron.
abstract: Although iron is required to sustain life, its free concentration and metabolism have to be tightly regulated. This is achieved through a variety of iron-binding proteins including transferrin and ferritin. During infection, bacteria acquire much of their iron from the host by synthesizing siderophores that scavenge iron and transport it into the pathogen. 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.
authors.affiliation: Institute for Systems Biology, Seattle, Washington 98103, USA.
authors.forename: Trude H
authors.initials: TH
authors.lastname: Flo
authors.forename: Kelly D
authors.initials: KD
authors.lastname: Smith
authors.forename: Shintaro
authors.initials: S
authors.lastname: Sato
authors.forename: David J
authors.initials: DJ
authors.lastname: Rodriguez
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Holmes
authors.forename: Roland K
authors.initials: RK
authors.lastname: Strong
authors.forename: Shizuo
authors.initials: S
authors.lastname: Akira
authors.forename: Alan
authors.initials: A
authors.lastname: Aderem
mesh_terms: D000209:Acute-Phase Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D004758:Enterobactin / Q000378:metabolism; D004926:Escherichia coli / Q000254:growth & development / Q000378:metabolism; D004927:Escherichia coli Infections / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D005260:Female; D007113:Immunity, Innate / Q000276:immunology*; D007501:Iron / Q000378:metabolism*; D000071068:Lipocalin-2; D054834:Lipocalins; D008297:Male; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D015513:Oncogene Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D013379:Substrate Specificity; D051193:Toll-Like Receptors
chemical_list: D000209:Acute-Phase Proteins; D000071068:Lipocalin-2; D054834:Lipocalins; D008562:Membrane Glycoproteins; D015513:Oncogene Proteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D051193:Toll-Like Receptors; C071332:Lcn2 protein, mouse; D004758:Enterobactin; D007501:Iron