Related Experiment Video
Updated: May 10, 2026

T4 Bacteriophage and E. coli Interaction in the Murine Intestine: A Prototypical Model for Studying Host-Bacteriophage Dynamics In Vivo
Published on: January 26, 2024
Short-term antagonism between bacteriophages and macrophages decreases with bacteria-phage coevolution
Meaghan Castledine1, Zuzanna Szczutkowska1, Andrew Matthews1
1Department of Ecology & Conservation, Environment and Sustainability Institute, University of Exeter, Penryn, Cornwall, TR10 9EZ, United Kingdom.
Abstract:
Phage therapy, the use of viruses that infect bacteria (bacteriophages), is a promising complement to antibiotics during the antimicrobial resistance crisis, but treatment success is very variable. A key variable, which likely influences treatment outcomes, is how different immune components interact with bacteriophage, with studies finding neutrophils work synergistically while macrophages work antagonistically with bacteriophage. However, many of these studies characterize interactions and outcomes over short timescales, not considering the potential for the evolution of resistance to bacteriophages which can itself greatly affect treatment outcomes. Here, we measure how macrophages and bacteriophages affect densities and resistance evolution of the pathogen Pseudomonas aeruginosa in vitro. Consistent with previous studies, we find macrophages interact antagonistically with bacteriophages in the short term. However, this antagonism was lost following bacterial population recovery associated with rapidly evolved resistance to bacteriophages. Macrophages resulted in greater net levels of resistance and hindered increases in bacteriophage infectivity, but this did not lead to differences in bacteria-phage population dynamics. This work emphasizes the importance of characterizing the effect of the immune system on phage therapy outcomes over both shorter- and longer- timescales.
Insights
Phage therapy success varies. Macrophages initially antagonize bacteriophages, but this effect disappears as bacteria evolve resistance, impacting overall treatment outcomes.
Area of Science:
- Microbiology
- Immunology
- Evolutionary Biology
Background:
- Antimicrobial resistance necessitates novel therapeutic strategies like phage therapy.
- Phage therapy involves using bacteriophages (viruses that infect bacteria) to combat bacterial infections.
- Immune system components, such as macrophages, can influence phage therapy efficacy, with variable short-term effects.
Purpose of the Study:
- To investigate the in vitro interactions between macrophages, bacteriophages, and the pathogen Pseudomonas aeruginosa.
- To assess the impact of these interactions on bacterial resistance evolution and population dynamics over time.
- To understand how short-term immune responses affect long-term phage therapy outcomes.
Main Methods:
- Culturing Pseudomonas aeruginosa in the presence of bacteriophages and macrophages.
- Monitoring bacterial and phage population densities over extended periods.
- Quantifying the evolution of bacteriophage resistance in bacterial populations.
Main Results:
- Macrophages exhibited short-term antagonism towards bacteriophages, consistent with prior research.
- This antagonism diminished as bacterial populations recovered due to the rapid evolution of bacteriophage resistance.
- Macrophages increased net bacterial resistance levels and limited bacteriophage infectivity gains, without altering overall population dynamics.
Conclusions:
- Immune cell interactions with bacteriophages are dynamic and change over time, particularly with the evolution of bacterial resistance.
- Short-term observations of immune-phage interactions may not accurately predict long-term phage therapy success.
- Characterizing immune system effects on phage therapy across both short and long timescales is crucial for optimizing treatment strategies.
Related Concept Videos
Lytic Cycle of Bacteriophages
Defense Against Bacterial Pathogens
Phagocytes
Phagocytes are the frontline soldiers of the immune system. They include neutrophils and macrophages. Neutrophils are the most abundant type of white blood cell and are quickly mobilized to the site of infection. Macrophages are larger cells that patrol...
Regulation of Bacterial Virulence
Microbial Interactions: Parasitism
Viral Replication: Lysogenic Cycle
Lysogenic Cycle of Bacteriophages

