期刊
JOURNAL OF LEUKOCYTE BIOLOGY
卷 92, 期 2, 页码 353-359出版社
WILEY
DOI: 10.1189/jlb.1111554
关键词
NF-kappa B; reactive nitrogen species; desferrioxamine; iron; siderophores
资金
- Austrian Science Fund (FWF) [TRP188]
- Verein zur Forderung von Forschung und Weiterbildung in Infektiologie und Immunologie an der Medizinischen Universitat Innsbruck
- U.S. National Institutes of Health [AI39557, AI48622, AI77629]
- Austrian Science Fund (FWF) [TRP188] Funding Source: Austrian Science Fund (FWF)
- Austrian Science Fund (FWF) [TRP 188] Funding Source: researchfish
The expression of the cation transporter Nramp1 (Slc11a1) in late phagolysosomes confers resistance to infection with several intracellular pathogens, such as Salmonella enterica, in mice. The antimicrobial actions of Nramp1 are attributable, in part, to modulation of macrophage immune function and cellular iron metabolism-the latter affecting the availability of the essential nutrient iron for intraphagosomal bacteria. Here, we provide novel evidence that Nramp1 functionality increases the expression of the peptide Lcn2, which exerts its antimicrobial activity by scavenging iron-loaded bacterial siderophores and mediating iron efflux from macrophages. With the use of macrophage cell lines expressing functional or nonfunctional Nramp1, we found significantly elevated Lcn2 mRNA and protein levels in Nramp1-expressing cells. These resulted from Nramp1-mediated alterations in the production of ROS, which stimulated NF-kappa B activity and subsequently, Lcn2 transcription. We observed that increased Lcn2 levels in primary Nramp1-positive macrophages resulted in a significant suppression of S. enterica serovar typhimurium growth. Stimulation of Lcn2 expression is a novel mechanism by which Nramp1 confers resistance against infection with the intracellular bacterium S. typhimurium. J. Leukoc. Biol. 92: 353-359; 2012.
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