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

Zhuoming Liu, Scott Reba, Wei Dong Chen, Suheel Kumar Porwal, W. Henry Boom, Robert B. Petersen, Roxana Rojas, Rajesh Viswanathan, L. Devireddy

Research output: Contribution to journalArticlepeer-review

43 Scopus citations

Abstract

Competition for iron influences host-pathogen interactions. Pathogens secrete small ironbinding moieties, siderophores, to acquire host iron. In response, the host secretes siderophorebinding 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.

Original languageEnglish
Pages (from-to)1197-1213
Number of pages17
JournalJournal of Experimental Medicine
Volume211
Issue number6
DOIs
StatePublished - Jun 2014

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