Hepcidin acts as both an
antimicrobial peptide and a hormonal regulator of
iron homeostasis; however, the
biological significance of this dual-function in immune reactions remains elusive. In this study, we provide experimental evidence regarding the coordination of this dual-function in the innate antimicrobial immunity using a zebrafish model. The transcription of
hepcidin gene was significantly upregulated in liver by Aeromonas hydrophila (A.
h) DNA stimulation, which was accompanied by an increase of
hepcidin protein and a decrease of
iron concentration in serum. Thus, an enhanced bactericidal activity against A.h and Escherichia coli and inhibitory effects on A.h growth and OmpA expression were observed in A.h cells, the latter of which made the bacterium more susceptible to
complement attack. The enhanced bacteriostatic activities in serum following the stimulation were dramatically impaired by neutralizing
hepcidin or restoring
iron to the samples. Immuno-protection assay showed that zebrafish administrated with A.
h DNA or designed CpG-ODNs had a significantly enhanced defence against A.h and Vibrio alginolyticus
infections, which was also eliminated by the neutralization of
hepcidin. Results indicate that the induction of
hepcidin leads to the decrease of
iron in circulation, which eventually limits
iron availability to invading microorganisms, thus contributing to host defence.