# Comparative analysis of immune responses to intraperitoneal administration of lytic E. coli bacteriophages in mice

## TL;DR

This study compares how different E. coli bacteriophages affect the immune system in mice, finding that one phage stimulates immune responses while others do not.

## Contribution

The study provides new insights into how specific lytic bacteriophages influence innate and adaptive immunity in mice.

## Key findings

- Phages vB_EcoM_SCS4 and vB_EcoM_SCS57 did not significantly alter immune responses in mice.
- Phage vB_EcoS_SCS44 stimulated innate and adaptive immunity, increasing cytokine expression and antibody titers.
- IFNγ gene expression and concentration were significantly increased by vB_EcoM_SCS4 and vB_EcoM_SCS57 phages.

## Abstract

•Lytic bacteriophages are a promising alternative to ineffective antibiotics.•In order to introduce phage therapy into widespread practice, studies on the effect of phages on patient immunity are needed.•The lytic phages Escherichia coli vB_EcoM_SCS4 and vB_EcoM_SCS57 were unable to significantly affect the immune responses of mice.•The lytic phage vB_EcoS_SCS44 was able to stimulate factors of innate and adaptive immunity in mice.

Lytic bacteriophages are a promising alternative to ineffective antibiotics.

In order to introduce phage therapy into widespread practice, studies on the effect of phages on patient immunity are needed.

The lytic phages Escherichia coli vB_EcoM_SCS4 and vB_EcoM_SCS57 were unable to significantly affect the immune responses of mice.

The lytic phage vB_EcoS_SCS44 was able to stimulate factors of innate and adaptive immunity in mice.

With the global spread of bacterial resistance and the decreasing effectiveness of antibiotics, the relevance of phage therapy is constantly growing. However, for systemic use of bacteriophages in medical practice, a complete understanding of their interaction not only with bacterial cells but also with human and animal organisms in the context of co-administered therapy is required.

This article presents the studies into the effects of lytic Escherichia coli bacteriophages on various immune response factors after their intraperitoneal administration in mice. It was found using Real-Time PCR and ELISA methods that the administration of the vB_EcoM_SCS4 and vB_EcoM_SCS57 phages did not increase the gene expression of TLR3, TLR9, IL-4, IL-5, IL-6 and the concentration of IL-2, IL-4, IL-5 and IL-6 in mice, but led to a multi-fold increase in the gene expression and concentration of IFNγ. Whereas, the injection of the vB_EcoS_SCS44 phage into mice increased the expression of the studied genes, except for the IL-5 gene, by 4 to 7 times and increased the concentration of IL-2, IL-4, IL-6 and IFNγ, except for IL-5, by 2 to 3 times. When determining the titer of virus-specific antibodies, it was found that after the administration of phages vB_EcoM_SCS4 and vB_EcoM_SCS57, the titer of IgA, IgG and IgM did not differ from that of the control animals, but the administration of phage vB_EcoS_SCS44 stimulated a twofold increase in the titer of phage-specific IgA, IgG, IgM.

Image, graphical abstract