Bacteriophages are well known for their therapeutic applicability. Although immense populations of phages are present in the human gut and other body sites, interactions with the human immune system have been ill-studied. Given the vast occurrence of phages, we wondered whether phages elicit immunomodulatory responses and more specifically whether they can suppress the immune system. This may explain how phages can be systemically active without inducing an immune response.

First, transcriptome analysis was carried out on human peripheral blood mononuclear cells (PBMCs) that were stimulated with a Pseudomonas aeruginosa phage lysate, thus containing bacterial proteins but no living or intact bacterial cells besides the infectious phage particles (comparable to conditions during phage therapy). Our results suggest that certain immunological pathways are activated during phage therapy (e.g. up-regulation of IL-10, SOCS3 and TNFA, and down-regulation of TGFBI). However, part of this interaction may result from bacterial fragment contamination.

Secondly, on the basis of these results, RT-qPCR analysis was performed for 10 of the most responsive immunity-related genes. In this context two different phage preparations (i.e. a phage lysate and a highly purified CsCl phage preparation) of four different P. aeruginosa phages and one S. aureus phage were evaluated for their immunological responses induced on the PBMCs. These analyses demonstrated comparable responses for the different phage preparations. These results indicate anti-inflammatory properties of phages.

The phage lysate preparation may closely reflect the immunological condition obtained during phage therapy, when the phage titer is the highest and only bacterial fragments remain. These results may provide a better insight into the efficacy and side effects of phage therapy.