Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2007-8-16
pubmed:abstractText
In being both, a modifier of cellular immune effector pathways and an essential nutrient for microbes, iron is a critical determinant in host-pathogen interaction. Here, we investigated the metabolic changes of macrophage iron homeostasis and immune function following the infection of RAW264.7 murine macrophages with Salmonella typhimurium. We observed an enhanced expression of the principal iron export protein, ferroportin 1, and a subsequent increase of iron efflux in Salmonella-infected phagocytes. In parallel, the expression of haem oxygenase 1 and of the siderophore-binding peptide lipocalin 2 was markedly enhanced following pathogen entry. Collectively, these modulations reduced both the cytoplasmatic labile iron and the ferritin storage iron pool within macrophages, thus restricting the acquisition of iron by intramacrophage Salmonella. Correspondingly, limitation of macrophage iron decreased microbial survival, whereas iron supplementation impaired immune response pathways in Salmonella-infected macrophages (nitric oxide formation and tumour necrosis factor-alpha production) and promoted intracellular bacterial proliferation. Our findings suggest that the enhancement of ferroportin 1-mediated iron efflux, the upregulation of the haem-degrading enzyme haem oxygenase 1 and the induction of lipocalin 2 following infection concordantly aim at withholding iron from intracellular S. typhimurium and to increase antimicrobial immune effector pathways thus limiting pathogen proliferation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Acute-Phase Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Antimicrobial Cationic Peptides, http://linkedlifedata.com/resource/pubmed/chemical/Cation Transport Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Ferritins, http://linkedlifedata.com/resource/pubmed/chemical/Heme Oxygenase-1, http://linkedlifedata.com/resource/pubmed/chemical/Iron, http://linkedlifedata.com/resource/pubmed/chemical/Lcn2 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Lipocalins, http://linkedlifedata.com/resource/pubmed/chemical/Oncogene Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha, http://linkedlifedata.com/resource/pubmed/chemical/hepcidin, http://linkedlifedata.com/resource/pubmed/chemical/metal transporting protein 1
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1462-5814
pubmed:author
pubmed:issnType
Print
pubmed:volume
9
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2126-40
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
The co-ordinated regulation of iron homeostasis in murine macrophages limits the availability of iron for intracellular Salmonella typhimurium.
pubmed:affiliation
Department of General Internal Medicine, Clinical Immunology and Infectious Diseases, Innsbruck Medical University, Innsbruck, Austria.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't