Immunomodulatory Effects of Escherichia coli Phage GADS24 on Human Dendritic Cells

TL;DR

This study shows that the E. coli phage GADS24 can modulate human dendritic cells, affecting their maturation and cytokine production, suggesting potential as a treatment for drug-resistant infections.

Contribution

The study introduces GADS24 as a novel phage with both antibacterial and immunomodulatory effects on dendritic cells.

Findings

GADS24 phage alone moderately upregulated DC maturation markers and altered cytokine production.

Combining bacterial lysate and phage reduced DC maturation compared to lysate alone.

Phage treatment decreased IL-10 and increased IL-12p70 secretion in dendritic cells.

Abstract

Background: Multidrug-resistant (MDR) Escherichia coli (E. coli) strains pose a significant public health challenge, which has led to the exploration of alternative therapeutic strategies. Due to their antibacterial and immunomodulatory properties, bacteriophages have emerged as promising therapeutic agents. Methods: This study investigates the effects of GADS24, a novel lytic bacteriophage of E. coli, on human-monocyte-derived dendritic cells (DCs). DCs are exposed to purified GADS24 phage, bacterial lysate, or a combination of both. Flow cytometry was used to assess the expression of surface markers (HLA-DR, CD80, CD83, and CD86), and ELISA was used to measure cytokine production (IL-10 and IL-12p70). Results: Following treatment with bacterial lysate, a significant increase in DC maturation markers was observed. The GADS24 phage alone induced a moderate upregulation of these markers, decreased IL-10 secretion, and increased IL-12p70. Combining bacterial lysate and phage tempered the maturation response compared to the lysate treatment alone. Conclusion: These findings suggest that GADS24 exerts antibacterial activity and modulates host immunity by influencing DC maturation and cytokine production. Due to its dual antimicrobial and immunomodulatory functions, GADS24 is likely to be a valuable adjunctive therapy for multidrug-resistant (MDR) bacterial infections. Furthermore, in vivo studies are necessary to confirm these promising in vitro results.

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