Iron depletion limits intracellular bacterial growth in macrophages

Prasad N. Paradkar et al. Blood 112, 866-874 (2008)

Speaker: Chih-Yu Huang (黃智郁)                                        Time:15:10-16:00, Nov. 26, 2008

Commentator: Dr. Jiunn-Jong Wu (吳俊忠老師)           Place: Room 601

Abstract:

    The use of iron as a cofactor in basic metabolic pathways is essential to both the pathogenic microorganisms and hosts. When the intracellular pathogens infect macrophages, they need to acquire iron for growth. In human, the iron concentration and fluxes are regulated at both the cellular and systemic levels. Ferroportin (Fpn), the only known cellular iron exporter, on macrophage plays an important role in iron recycling. On the other hand hepcidin, an antimicrobial peptide secreted by hepatocytes in response to inflammatory stimuli, helps destruction of the invading microorganisms during infection. Hepcidin can also inhibit cellular iron efflux through binding to and inducing the degradation of Fpn that consequently lead to a decrease in serum iron level¹. This is probably another host defense mechanism to limit the acquisition of iron by invading microorganisms. However, the increasing iron load in macrophages during infection may raise another risk of infection by intracellular pathogens. To test this hypothesis, the authors used three intracellular bacteria, Chlamydia psittaci, C. trachomatis and Legionella pneumophila, to show that the growth of these bacteria was indeed promoted by hepcidin-mediated down-regulation of ferroportin. Further, by treatment with the clinically used iron chelators especially the two oral iron chelators deferriprone (L1) and desferasirox (ICL670A), the intracellular iron concentration and growth of these intracellular bacteria were suppressed. These results suggest that these iron chelators might be therapeutic in the chronic intracellular bacterial infections.

Reference:

1.          Elizabeta Nemeth, et al. Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science 306, 2090-2093 (2004).