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Updated: Apr 25, 2026
An In vitro Model to Study Immune Responses of Human Peripheral Blood Mononuclear Cells to Human Respiratory Syncytial Virus Infection
Published on: December 10, 2013
Dual stimulation with bacterial and viral components increases the expression of hepcidin in human monocytes
Delia A Ripley1, Roger H Morris, Sarah E Maddocks
1Cardiff School of Health Sciences, Cardiff Metropolitan University, Cardiff, UK.
Abstract:
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.
Insights
Hepcidin, an antimicrobial peptide regulating iron, significantly increases during combined bacterial and viral infections. It also shows antagonistic effects with antibiotics against key bacteria, impacting future antimicrobial resistance treatments.
Area of Science:
- Immunology
- Microbiology
- Biochemistry
Background:
- Hepcidin is a key regulator of iron metabolism and an antimicrobial peptide (AMP).
- Antimicrobial peptides can possess dual roles, including antimicrobial and immunoregulatory functions.
- Toll-like receptors (TLRs) are crucial in innate immunity, recognizing microbial components and initiating signaling pathways.
Purpose of the Study:
- To investigate the role of hepcidin in combined infections.
- To evaluate the effect of Toll-like receptor (TLR) co-stimulation on hepcidin expression.
- To assess the combined effect of hepcidin and antibiotics against bacterial pathogens.
Main Methods:
- THP-1-derived monocytes were co-stimulated with TLR3 (poly I:C) and TLR9 (CpG) ligands.
- Hepcidin expression levels were quantified 24 hours post-stimulation.
- A chequerboard assay was employed to determine the fractional inhibitory concentration index (FICI) of hepcidin in combination with antibiotics against Staphylococcus aureus, Pseudomonas aeruginosa, and Streptococcus pyogenes.
Main Results:
- Co-stimulation with poly I:C and CpG ligands significantly increased hepcidin expression (10-fold) compared to untreated controls.
- Hepcidin demonstrated an antagonistic effect when combined with rifampicin and tetracycline against S. aureus, P. aeruginosa, and S. pyogenes (FICI > 4).
Conclusions:
- Hepcidin plays a potential role in host defense during simultaneous bacterial and viral infections.
- The antagonistic interaction between hepcidin and certain antibiotics suggests caution in combination therapies.
- Findings have significant implications for developing novel treatment strategies in the context of rising antimicrobial resistance.
