Show simple item record

dc.contributor.authorSteigedal, Magnus
dc.contributor.authorMarstad, Anne
dc.contributor.authorHaug, Markus
dc.contributor.authorDamås, Jan Kristian
dc.contributor.authorStrong, Roland K.
dc.contributor.authorRoberts, Pacita L.
dc.contributor.authorHimpsl, Stephanie D.
dc.contributor.authorStapleton, Ann
dc.contributor.authorHooton, Thomas M.
dc.contributor.authorMobley, Harry L.T.
dc.contributor.authorHawn, Thomas R.
dc.contributor.authorFlo, Trude Helen
dc.date.accessioned2017-11-15T09:17:14Z
dc.date.available2017-11-15T09:17:14Z
dc.date.created2015-01-07T13:25:37Z
dc.date.issued2014
dc.identifier.citationJournal of Immunology. 2014, 193 (12), 6081-6089.nb_NO
dc.identifier.issn0022-1767
dc.identifier.urihttp://hdl.handle.net/11250/2466350
dc.description.abstractCompetition for iron is a critical component of successful bacterial infections, but the underlying in vivo mechanisms are poorly understood. We have previously demonstrated that lipocalin 2 (LCN2) is an innate immunity protein that binds to bacterial siderophores and starves them for iron, thus representing a novel host defense mechanism to infection. In the present study we show that LCN2 is secreted by the urinary tract mucosa and protects against urinary tract infection (UTI). We found that LCN2 was expressed in the bladder, ureters, and kidneys of mice subject to UTI. LCN2 was protective with higher bacterial numbers retrieved from bladders of Lcn2-deficient mice than from wild-type mice infected with the LCN2-sensitive Escherichia coli strain H9049. Uropathogenic E. coli mutants in siderophore receptors for salmochelin, aerobactin, or yersiniabactin displayed reduced fitness in wild-type mice, but not in mice deficient of LCN2, demonstrating that LCN2 imparts a selective pressure on bacterial growth in the bladder. In a human cohort of women with recurrent E. coli UTIs, urine LCN2 levels were associated with UTI episodes and with levels of bacteriuria. The number of siderophore systems was associated with increasing bacteriuria during cystitis. Our data demonstrate that LCN2 is secreted by the urinary tract mucosa in response to uropathogenic E. coli challenge and acts in innate immune defenses as a colonization barrier that pathogens must overcome to establish infection.nb_NO
dc.language.isoengnb_NO
dc.publisherThe American Association of Immunologistsnb_NO
dc.titleLipocalin 2 imparts selective pressure on bacterial growth in the bladder and is elevated in women with urinary tract infectionnb_NO
dc.typeJournal articlenb_NO
dc.typePeer reviewednb_NO
dc.description.versionpublishedVersionnb_NO
dc.source.pagenumber6081-6089nb_NO
dc.source.volume193nb_NO
dc.source.journalJournal of Immunologynb_NO
dc.source.issue12nb_NO
dc.identifier.doi10.4049/jimmunol.1401528
dc.identifier.cristin1192406
dc.relation.projectNorges forskningsråd: 180578nb_NO
dc.relation.projectNorges forskningsråd: 223255nb_NO
dc.description.localcode© 2014 by The American Association of Immunologists, Inc. This is a published Author Choice article (paid immediate Open Access). The definitive published version is available at https://doi.org/10.4049/jimmunol.1401528nb_NO
cristin.unitcode194,65,15,30
cristin.unitcode194,65,15,0
cristin.unitnameCentre of Molecular Inflammation Research (SFF-CEMIR)
cristin.unitnameInstitutt for kreftforskning og molekylær medisin
cristin.ispublishedtrue
cristin.fulltextpostprint
cristin.fulltextpreprint
cristin.qualitycode2


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record