# Bacteriophages JEP7 and PBC2, which target foodborne pathogens, elicit cytokine responses in mammalian cells

## TL;DR

This study shows that certain bacteriophages can trigger inflammatory responses in mammalian cells by inducing cytokine production.

## Contribution

The study identifies specific phages that induce cytokine responses in mammalian cells, suggesting a potential link between phage exposure and inflammation.

## Key findings

- Escherichia coli phage JEP7 stimulates TNF-α, IL-6, and IL-10 in RAW 264.7 cells.
- Bacillus cereus phage PBC2 induces IL-10 in RAW 264.7 cells and differentially affects cytokine levels in Caco-2 cells.
- Phage internalization, cytotoxicity, and glycosylation do not significantly influence cytokine induction.

## Abstract

Phage therapy provides a potential approach to combat foodborne pathogens, yet the impact of phages on mammalian immune responses remains insufficiently explored. This study investigated the effects of ten phages on inflammatory cytokine production in RAW 264.7 macrophages and Caco-2 cells. Escherichia coli phage JEP7 stimulated TNF-α, IL-6, and IL-10, while Bacillus cereus phage PBC2 induced IL-10 in RAW 264.7 cells. JEP7 and PBC2 also differentially induced TNF-α, IL-6, and IL-10 expression in Caco-2 cells, reaching levels comparable to those triggered by lipopolysaccharide, demonstrating cytokine production across cell types. Comparative analysis of phage internalization, cytotoxicity, and virion glycosylation revealed no differences between cytokine-inducing and non-inducing phages, suggesting that these factors do not significantly impact inflammatory responses induced by JEP7 and PBC2. These findings demonstrate that phages might stimulate inflammatory responses via differential cytokine induction, although common factors affecting immune responses among the analyzed phages remain unidentified and warrant further investigation.

The online version contains supplementary material available at 10.1007/s10068-025-02042-3.