Lipocalin 2 Mediates an Innate Immune Response to Bacterial Infection by Sequestrating Iron

Nature. 2004 Dec 16;432(7019):917-21. doi: 10.1038/nature03104. Epub 2004 Nov 7.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute-Phase Proteins / deficiency
  • Acute-Phase Proteins / genetics
  • Acute-Phase Proteins / metabolism*
  • Animals
  • Enterobactin / metabolism
  • Escherichia coli / growth & development
  • Escherichia coli / metabolism
  • Escherichia coli Infections / immunology*
  • Escherichia coli Infections / metabolism
  • Escherichia coli Infections / microbiology
  • Female
  • Immunity, Innate / immunology*
  • Iron / metabolism*
  • Lipocalin-2
  • Lipocalins
  • Male
  • Membrane Glycoproteins / deficiency
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Oncogene Proteins / deficiency
  • Oncogene Proteins / genetics
  • Oncogene Proteins / metabolism*
  • Protein Binding
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Cell Surface / deficiency
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism
  • Substrate Specificity
  • Toll-Like Receptors

Substances

  • Acute-Phase Proteins
  • Lipocalin-2
  • Lipocalins
  • Membrane Glycoproteins
  • Oncogene Proteins
  • RNA, Messenger
  • Receptors, Cell Surface
  • Toll-Like Receptors
  • Lcn2 protein, mouse
  • Enterobactin
  • Iron