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

Nature 2004

Speaker : 林嬿琳                          Time : 14:00-15:00, Dec. 22, 2004

Commentator : 吳俊忠 老師                 Place : Room 601

Abstract :

Although iron is essential for the host and the pathogen, as both require this metal as a cofactor or as a prosthetic group for essential enzymes, its free concentration is limited in the host. During infection, bacteria synthesize and secrete siderophores, low-molecular-mass microbial compounds with the very high affinity for iron, to acquire iron and transport it into bacteria.  The authors have demonstrated that enterochelin, a bacterial catecholate siderophore, bind to the host lipocalin 2. Therefore, they proposed that lipocalin2 participated in the antibacterial iron sequestration strategy of the innate immune system. They found that lipocalin 2 is strongly induced by TLR stimuli, and it has important function in innate defence against bacterial infections. Lipocalin 2 inhibited the growth of the clinical strain of Escherichia coli. H9049. However, ferrichrome, a hydroxamate-type siderophore, not synthesized by E. coli H9049, but can be used by the bacterium, was able to circumvent lipocalin 2 dependent bacteriostatic action. On the contrary, the growth of Staphylococcus aureus did not require enterochelin-type siderophores, neither affected by the addition of lipocalin 2. These results demonstrate that lipocalin 2 confers resistance to bacterial infection by abrogating enterochelin-like, siderophore-dependent iron uptake.  In the mouse model, the data indicate that the absence of this defense mechanism can lead to bacteraemia and sepsis. Therefore, these findings may have implications for the clinical treatment of bacteraemia and sepsis caused by E. coli.

References :

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3. Flo T. H. et al. Lipocalin 2 mediates an innate immune response to bacterial infection by sequestrating iron. Nature 1-5 (2004).