Regulation of mammalian siderophore 2,5-DHBA in the innate immune response to infection

• Published in: The Journal of experimental medicine Vol. 211; no. 6; pp. 1197 - 1213
• Main Authors: Liu, Zhuoming, Reba, Scott, Chen, Wei-Dong, Porwal, Suheel Kumar, Boom, W Henry, Petersen, Robert B, Rojas, Roxana, Viswanathan, Rajesh, Devireddy, L
• Format: Journal Article
• Language: English
• Published: United States The Rockefeller University Press 02.06.2014
• Subjects: Acute-Phase Proteins - genetics; Acute-Phase Proteins - immunology; Acute-Phase Proteins - metabolism; Animals; Bacterial Infections - genetics; Bacterial Infections - immunology; Bacterial Infections - metabolism; Bacterial Outer Membrane Proteins - genetics; Bacterial Outer Membrane Proteins - immunology; Bacterial Outer Membrane Proteins - metabolism; Candida albicans - immunology; Candida albicans - physiology; Candidiasis - genetics; Candidiasis - immunology; Candidiasis - metabolism; Carrier Proteins - genetics; Carrier Proteins - immunology; Carrier Proteins - metabolism; Cell Line; Enterobactin - immunology; Enterobactin - metabolism; Escherichia coli - genetics; Escherichia coli - immunology; Escherichia coli - physiology; Female; Gentisates - immunology; Gentisates - metabolism; Hydroxybutyrate Dehydrogenase - genetics; Hydroxybutyrate Dehydrogenase - immunology; Hydroxybutyrate Dehydrogenase - metabolism; Immunity, Innate - genetics; Immunity, Innate - immunology; Immunoblotting; Kaplan-Meier Estimate; Lipocalin-2; Lipocalins - genetics; Lipocalins - immunology; Lipocalins - metabolism; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mutation - immunology; Oncogene Proteins - genetics; Oncogene Proteins - immunology; Oncogene Proteins - metabolism; Positive Regulatory Domain I-Binding Factor 1; Receptors, Cell Surface - genetics; Receptors, Cell Surface - immunology; Receptors, Cell Surface - metabolism; Reverse Transcriptase Polymerase Chain Reaction; RNA Interference; Siderophores - immunology; Siderophores - metabolism; Staphylococcus aureus - immunology; Staphylococcus aureus - physiology; Transcription Factors - genetics; Transcription Factors - immunology; Transcription Factors - metabolism
• ISSN: 0022-1007; 1540-9538
• DOI: 10.1084/jem.20132629

Competition for iron influences host-pathogen interactions. Pathogens secrete small iron-binding moieties, siderophores, to acquire host iron. In response, the host secretes siderophore-binding proteins, such as lipocalin 24p3, which limit siderophore-mediated iron import into bacteria. Mammals produce 2,5-dihydroxy benzoic acid, a compound that resembles a bacterial siderophore. Our data suggest that bacteria use both mammalian and bacterial siderophores. In support of this idea, supplementation with mammalian siderophore enhances bacterial growth in vitro. In addition, mice lacking the mammalian siderophore resist E. coli infection. Finally, we show that the host responds to infection by suppressing siderophore synthesis while up-regulating lipocalin 24p3 expression via TLR signaling. Thus, reciprocal regulation of 24p3 and mammalian siderophore is a protective mechanism limiting microbial access to iron.