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Dual stimulation with bacterial and viral components increases the expression of hepcidin in human monocytes

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posted on 2022-04-08, 15:27 authored by Delia A. Ripley, Keith Morris, Sarah Maddocks

 Hepcidin belongs to the antimicrobial peptide (AMP) family and is the key regulator of iron metabolism. It modulates iron homeostasis by binding to, and degrading the iron exporter molecule, ferroportin, thus inhibiting cellular iron efflux. Many antimicrobial peptides have a dual function; some are able to act directly as an antimicrobial agent as well as having an immunoregulatory role in the host. Toll-like receptors (TLRs) bind to components of microorganisms, activate cellular signal transduction pathways and stimulate innate immune responses. The effect of TLR3 (poly I:C) and TLR9 (CpG) co-stimulation of THP-1-derived monocytes using purified TLR ligands showed that 24 h after exposure poly I:C and CpG ligands in combination, hepcidin expression was significantly increased (10-fold) when compared to the untreated control. This combination of TLR ligands mimics simultaneous bacterial and viral infections, thus suggesting a potential key role for hepcidin in combined infections. Additionally, using a chequerboard assay, we have shown that hepcidin has an antagonistic effect in combination with the antibiotics rifampicin and tetracycline against Staphylococcus aureus, Pseudomonas aeruginosa and Streptococcus pyogenes, evidenced by a fractional inhibitory concentration index (FICI) > 4. This finding has important implications for future treatment regimens especially in an era of increasing antimicrobial resistance. 

History

Published in

FEMS Microbiology Letters

Publisher

Wiley

Version

  • AM (Accepted Manuscript)

Citation

Ripley, D. A., Morris, R. H. and Maddocks, S. E. (2014), 'Dual stimulation with bacterial and viral components increases the expression of hepcidin in human monocytes', FEMS Microbiology Letters, 359, pp. 161–165

Print ISSN

0378-1097

Cardiff Met Affiliation

  • Cardiff School of Sport and Health Sciences

Cardiff Met Authors

Keith Morris Sarah Maddocks

Cardiff Met Research Centre/Group

  • Microbiology & Infection

Copyright Holder

  • © The Publisher

Language

  • en

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