1. Institute for Systems Biology, Seattle, Washington 98103, USA
2. Institute for Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, 7489 Trondheim, Norway
3. University of Washington, Department of Pathology, Seattle, Washington 98195, USA
4. Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, and Exploratory Research for Advanced Technology (ERATO), Japan Science and Technology Corporation, Osaka 565-0871, Japan
5. Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA
6. These authors contributed equally to this work

Correspondence to: Alan Aderem¹ Email: aaderem@systemsbiology.org

Abstract

Although iron is required to sustain life, its free concentration and metabolism have to be tightly regulated¹. This is achieved through a variety of iron-binding proteins including transferrin and ferritin². 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.

1. Institute for Systems Biology, Seattle, Washington 98103, USA
2. Institute for Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, 7489 Trondheim, Norway
3. University of Washington, Department of Pathology, Seattle, Washington 98195, USA
4. Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, and Exploratory Research for Advanced Technology (ERATO), Japan Science and Technology Corporation, Osaka 565-0871, Japan
5. Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA
6. These authors contributed equally to this work

Correspondence to: Alan Aderem¹ Email: aaderem@systemsbiology.org

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