The effects of T4 and A5/80 phages on the expression of immunologically important genes in differentiated Caco-2 cells*

Introduction: Bacteriophages are an abundant component of the mucosal microbiota in humans and some animal species. Intestinal epithelial cells (IECs) are the key element responsible for the induction and regulation of immune responses in the gut mucosa. The objective of this study was to evaluate the effects of T4 and A5/80 bacteriophages on the expression of immunologically important genes in Caco-2, a model cell line for IECs. Materials & Method: Bacteriophages were added to cultures of differentiated Caco-2 cells for 12 hours, while control cultures were treated with phosphate-buffered saline (PBS). Expression of genes in Caco-2 cells was determined using custom-made RT2 Profiler PCR Arrays, which allow for the evaluation of gene expression with the sensitivity and specificity of real-time PCR. We evaluated the expression of 21 genes which are important for the immune functions of IECs, including IL1B, IL6, IL7, IL10, IL15, IL18, IL25, IL33, TGFB1, TNF, CXCL8, CCL2, TSLP, FCER2, PIGR, DEFB4A, CAMP, REG3G, TNFSF13, TNFSF13B, and MUC2. Results: Both examined phages significantly influenced the expression of a number of genes compared with control cultures. In particular, T4 significantly increased the expression of the CCL2 and DEFB4A genes, while A5/80 induced the expression of the PIGR gene. Discussion: Together with the findings from previous studies, our results suggest that by modulating the expression of some genes, bacteriophages may affect immune responses in the gut mucosa.