Bacteriophages (or phages) are viruses that infect, replicate in, and can kill bacteria. They can have utility as alternatives to antibacterial drugs. Phages have bacterial specificity, and have not been found to infect eukaryotic cells. Given these attributes, phages may be suitable candidates for the treatment of bacterial infections without affecting mammalian cells or beneficial microflora. Furthermore, there is data that show that oral ingestion of phages by animals leads to entry of the phages into the bloodstream and reach internal tissues.
A study was conducted to examine the gene expression profile of peripheral blood mononuclear cells from six human donors for twelve immunity-related genes (CD14, CXCL1, CXCL5, IL1A, IL1B, IL1RN, IL6, IL10, LYZ, SOCS3, TGFBI and TNFA) induced by Staphylococcus aureus phage ISP and four Pseudomonas aeruginosa phages. Stimulation of peripheral blood mononuclear cells with either an S. aureus phage ISP lysate, the highly purified phage ISP, or the S. aureus host strain showed that the highly purified phage ISP significantly upregulated the CXCL1, IL1A, IL1B, IL1RN, IL6 and TNFA genes and down-regulated CD14, LYZ and TGFBI compared to the phage lysate. The immune response induced by the phage ISP and the S. aureus host showed strong down-regulation of LYZ gene expression.
The peripheral blood mononuclear cells were stimulated with either saline, P. aeruginosa strains, or P. aeruginosa phage PNM. Transcriptome analysis of the unstimulated peripheral blood mononuclear cells compared to those stimulated with P. aeruginosa strain 573 revealed upregulation of 996 genes and downregulation of 1377 genes. Stimulation of peripheral blood mononuclear cells with P. aeruginosa phage PNM led to upregulation of 704 and downregulation of 392 genes. Many of the differentially expressed genes have immunity-related functions.
For P. aeruginosa phages PNM, LUZ19, 14-1 and GE_vB_Pae-Kakheti25, the phage lysate induced a stronger immune response compared to the highly purified phage. The overall immune response for all five phages were consistent, and it appears that the studied phages have pro- and anti-inflammatory properties. The anti-inflammatory effects of phages predominate and may allow them to reduce bacterial numbers and combat infection, while limiting adverse effects on an individual.
Van Belleghem, J., Clement, F., Merabishvili, M., Lavigne, R., & Vaneechoutte, M. (2017). Pro- and anti-inflammatory responses of peripheral blood mononuclear cells induced by Staphylococcus aureus and Pseudomonas aeruginosa phages. Scientific Reports, 7(1). doi:10.1038/s41598-017-08336-9