Abstract
The objective of this study was to evaluate the effects of A3R phage and Staphylococcus aureus lysate obtained after phage infection on neutrophil degranulation. The exocytosis of primary and secondary granules from neutrophils was investigated in vitro in whole blood specimens by flow cytometry based on the expression of specific markers of exocytosis (CD63 for primary granules and CD66b for secondary granules). We found that both A3R and S. aureus lysate had no significant effect on the exocytosis of primary and secondary granules. These data suggest that neither A3R virions nor any products of phage-induced lysis of S. aureus are likely to induce neutrophil degranulation in patients who are treated with phage preparations. Since neutrophil granules contain some potentially toxic proteins, our results provide an important argument for the safety of phage therapy. Moreover, these data indicate that the induction of neutrophil degranulation is not likely to contribute to antibacterial effects of phages.
Highlights
While phages are unable to infect eukaryotic cells, many studies have shown that they can interact with some types of these cells, especially with those of the immune system
To determine the effects of A3R phage and S. aureus lysate on neutrophil degranulation, we evaluated the expression of two degranulation markers—CD63 and CD66b
Unlike A3R, heat-inactivated S. aureus cells used as the positive control markedly increased the Unlike A3R, heat‐inactivated S. aureus cells used as the positive control8 markedly increased the percentage of CD63+ neutrophils
Summary
While phages are unable to infect eukaryotic cells, many studies have shown that they can interact with some types of these cells, especially with those of the immune system. Phages were shown to influence functions of different types of immune cells involved in the induction of both innate and adaptive immune responses including dendritic cells (DCs), monocytes, neutrophils, as well as T- and. Research on the interactions between phages and immune cells is important to understand the fate of phage virions in the organism of a patient treated with phage preparations. These studies are essential for verification of the safety of therapeutic use of phages, since potential activation of immune cells could result in side-effects of phage therapy. Excessive activation of some neutrophil functions by phages (or some products of phage-induced lysis of bacterial cells) could cause damage to tissues following the administration of phage preparations
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