Iron‐depletion limits intracellular bacterial growth in macrophages

Abstract

Many intracellular pathogens are known to infect macrophages and these pathogens require iron for growth. Here we demonstrate in vitro that the intracellular growth of Chlamydia psittaci, Chlamydia trachomatis and Legionella pneumophila is regulated by the levels of intracellular iron. Macrophages that express cell surface ferroportin, the only known iron exporter, limit the intracellular growth of these bacteria. Hepcidin is an anti‐microbial peptide secreted by the liver in response to inflammation. Hepcidin binds to ferroportin mediating its internalization and degradation. Changes in ferroportin levels are of particular importance in macrophages as they are continually turning over red blood cells and thus acquiring iron. Addition of the exogenous hepcidin to infected macrophages enhanced the intracellular growth of these pathogens. Flatiron mouse macrophages, a mouse model of Ferroportin disease, showed enhanced intracellular bacterial growth independent of the presence of exogenous hepcidin. Macrophages, from wild type or flatiron mice, incubated with the oral iron chelators deferriprone or desferasirox showed reduced intracellular bacterial growth suggesting that these chelators might be therapeutic in chronic intracellular bacterial infections.