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Updated: Jul 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
Bacteriophage preparation inhibition of reactive oxygen species generation by endotoxin-stimulated polymorphonuclear
Ryszard Miedzybrodzki1, Kinga Switala-Jelen, Wojciech Fortuna
1Bacteriophage Laboratory, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Rudolfa Weigla 12, 53-114 Wroclaw, Poland. mbrodzki@iitd.pan.wroc.pl
Abstract:
It has been known that administration of antibiotics may lead to excessive release of bacterial endotoxins and complicate clinical course of patients with Gram-negative infections. This concern may also apply to phages. Endotoxin may in turn activate neutrophils to produce reactive oxygen species (ROS) that are believed to play an important role in the pathogenesis of multiple organ dysfunction in the course of sepsis. We showed that a purified T4 phage preparation with low-endotoxin content could significantly diminish the luminol-dependent chemiluminescence (CL) of peripheral blood polymorphonuclear leukocytes (PMNs) both stimulated by lipopolysaccharides (LPSs) isolated from different Escherichia coli strains. This effect was also observed for live bacteria used for PMNs stimulation and was independent of bacterial susceptibility for T4-mediated lysis. Our data suggest, that phage-mediated inhibition of LPS- or bacteria-stimulated ROS production by PMNs may be attributed not only to phage-PMNs interactions, but also to phage-LPS interactions and bacterial lysis (in case of homologous phage). Interestingly, the T4 preparation did not influence ROS formation by PMNs stimulated with PMA. This suggests that the observed phenomena are also dependent upon the nature of activator. Bacteriophage-mediated inhibition of ROS formation by cells exposed to endotoxin provides new evidence for possible interactions between phages and mammalian cells. It helps in understanding the role of phages in our environment and may also be of important clinical significance.
Insights
Bacteriophages can reduce harmful reactive oxygen species (ROS) produced by neutrophils responding to endotoxins from Gram-negative bacteria. This phage-mediated inhibition of ROS offers new insights into phage-host interactions and potential clinical applications.
Area of Science:
- Microbiology
- Immunology
- Biochemistry
Background:
- Antibiotic use can worsen Gram-negative infections via endotoxin release.
- Endotoxins activate neutrophils, producing reactive oxygen species (ROS) implicated in sepsis pathogenesis.
- Bacteriophages, viruses that infect bacteria, may also interact with host immune responses.
Purpose of the Study:
- To investigate the effect of purified T4 bacteriophage preparations on neutrophil ROS production stimulated by endotoxins.
- To explore potential mechanisms behind phage-mediated modulation of immune cell responses.
Main Methods:
- Purified T4 bacteriophage preparation with low endotoxin content was used.
- Luminol-dependent chemiluminescence (CL) measured ROS production by peripheral blood polymorphonuclear leukocytes (PMNs).
- PMNs were stimulated with lipopolysaccharides (LPSs) from Escherichia coli and live bacteria.
Main Results:
- T4 phage preparation significantly diminished LPS-stimulated ROS production by PMNs.
- This inhibitory effect was also observed with live bacteria, independent of phage lysis.
- Phage preparation did not affect ROS production stimulated by phorbol myristate acetate (PMA), indicating activator-dependent effects.
Conclusions:
- Bacteriophage-mediated inhibition of ROS production by PMNs exposed to endotoxin is demonstrated.
- Mechanisms may involve phage-host cell and phage-LPS interactions, as well as bacterial lysis.
- These findings highlight novel interactions between bacteriophages and mammalian cells with potential clinical significance.
