Lipocalin 2 (Lcn2) interferes with iron uptake by Brucella abortus and dampens immunoregulation during infection of RAW 264.7 macrophages

Cell Microbiol. 2018 Mar;20(3). doi: 10.1111/cmi.12813. Epub 2017 Dec 18.


Lipocalin 2 (Lcn2) is an important innate immunity component against bacterial pathogens. In this study, we report that Lcn2 is induced by Brucella (B.) abortus infection and significantly contributes to the restriction of intracellular survival of Brucella in macrophages. We found that Lcn2 prevented iron uptake by B. abortus through two distinct mechanisms. First, Lcn2 is secreted to capture bacterial siderophore(s) and abrogate iron import by Brucella. Second, Lcn2 decreases the intracellular iron levels during Brucella infection, which probably deprives the invading Brucella of the iron source needed for growth. Suppression of Lcn2 signalling resulted in a marked induction of anti-inflammatory cytokine, interleukin 10, which was shown to play a major role in Lcn2-induced antibrucella immunity. Similarly, interleukin 6 was also found to be increased when Lcn2 signalling is abrogated; however, this induction was thought to be an alternative pathway that rescues the cell from infection when the effective Lnc2 pathway is repressed. Furthermore, Lcn2 deficiency also caused a marked decrease in brucellacidal effectors, such as reactive oxygen species and nitric oxide but not the phagolysosome fusion. Taken together, our results indicate that Lcn2 is required for the efficient restriction of intracellular B. abortus growth that is through limiting iron acquisition and shifting cells to pro-inflammatory brucellacidal activity in murine macrophages.

Keywords: Brucella abortus; NO; ROS; apoptosis; iron sequestrating; lipocalin 2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brucella abortus / immunology
  • Brucella abortus / metabolism*
  • Brucella abortus / pathogenicity
  • Cation Transport Proteins / metabolism
  • Immunity, Innate / physiology
  • Iron / metabolism*
  • Lipocalin-2 / metabolism*
  • Macrophages / metabolism
  • Macrophages / microbiology
  • Mice
  • RAW 264.7 Cells


  • Cation Transport Proteins
  • Lipocalin-2
  • metal transporting protein 1
  • Iron