Iron depletion limits intracellular bacterial growth in macrophages.
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.
Paradkar
Prasad N
PN
Department of Pathology, School of Medicine, University of Utah, Salt Lake City, Utah 84132, USA.
De Domenico
Ivana
I
Durchfort
Nina
N
Zohn
Irene
I
Kaplan
Jerry
J
Ward
Diane McVey
DM
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
D023181:Antimicrobial Cationic Peptides; D027682:Cation Transport Proteins; C579599:Hamp protein, mouse; D064451:Hepcidins; D007502:Iron Chelating Agents; D000098742:Ferroportin