title: Iron depletion limits intracellular bacterial growth in macrophages.
abstract: Many intracellular pathogens infect macrophages and these pathogens require iron for growth. Here we demonstrate in vitro that the intracellular growth of Chlamydia psittaci, trachomatis, and Legionella pneumophila is regulated by the levels of intracellular iron. Macrophages that express cell surface ferroportin, the only known cellular iron exporter, limit the intracellular growth of these bacteria. Hepcidin is an antimicrobial peptide secreted by the liver in response to inflammation. Hepcidin binds to ferroportin mediating its internalization and degradation. Addition of hepcidin to infected macrophages enhanced the intracellular growth of these pathogens. Macrophages from flatiron mice, a strain heterozygous for a loss-of-function ferroportin mutation, showed enhanced intracellular bacterial growth independent of the presence of exogenous hepcidin. Macrophages, from wild-type or flatiron mice, incubated with the oral iron chelator deferriprone or desferasirox showed reduced intracellular bacterial growth suggesting that these chelators might be therapeutic in chronic intracellular bacterial infections.
authors: Department of Pathology, School of Medicine, University of Utah, Salt Lake City, Utah 84132, USA.
authors: Prasad N
authors: PN
authors: Paradkar
authors: Ivana
authors: I
authors: De Domenico
authors: Nina
authors: N
authors: Durchfort
authors: Irene
authors: I
authors: Zohn
authors: Jerry
authors: J
authors: Kaplan
authors: Diane McVey
authors: DM
authors: Ward
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology; D001419:Bacteria / Q000254:growth & development*; D027682:Cation Transport Proteins / Q000378:metabolism; D002478:Cells, Cultured; D002692:Chlamydia trachomatis; D002691:Chlamydophila psittaci; D064451:Hepcidins; D007502:Iron Chelating Agents / Q000494:pharmacology; D000090463:Iron Deficiencies; D016952:Legionella pneumophila; D008264:Macrophages / Q000382:microbiology*; D051379:Mice; D000098742:Ferroportin
chemical_list: D023181:Antimicrobial Cationic Peptides; D027682:Cation Transport Proteins; C579599:Hamp protein, mouse; D064451:Hepcidins; D007502:Iron Chelating Agents; D000098742:Ferroportin