Effect of phage therapy on the turnover and function of peripheral neutrophils

Abstract

The aim of this investigation was to establish the impact of phage therapy on the turnover and function of circulating neutrophils in 37 patients with suppurative bacterial infections. We determined the levels of circulating neutrophils and their precursors before therapy, after 3 weeks of therapy, and at a distant time interval (3 months) following the beginning of therapy. In addition, we measured the ability of neutrophils to phagocytize Staphylococcus aureus in vitro. Eight healthy blood donors served as a control group. The results showed that, among the studied parameters, the significant changes involved neutrophil precursor count and the ability of neutrophils to phagocytize bacteria. The percentage of neutrophils in patients before therapy was lower than in healthy donors (mean 58.0, versus 61.4). This value dropped further in patients after 3 months of following the therapy (mean 55.6). The content of neutrophil precursors, on the other hand, was lower in healthy donors than in patients before therapy (mean 2.5, versus 3.8). After 3 weeks of the therapy and after 3 months, the levels of neutrophil precursors were significantly higher (mean 4.8 and 4.9, respectively) than in control donors. The phagocytic index was lower in patients before therapy than in control donors (mean 66.3, versus 70.1) and decreased further after 3 weeks of therapy (mean 59.0) and after 3 months (mean 59.6). The results of this investigation indicate that successful phage therapy accelerates the turnover of neutrophils, accompanied by a decrease in their ability to phagocytize bacteria.

Effects of bacteriophages on free radical production and phagocytic functions

“…Nevertheless, these phenomena apparently did not interfere with the healing process. On the other hand, an increased number of circulating precursors of neutrophils [36] and a normalization of the cytokine production [35] in these patients were found. It could be possible that the decreased capability of neutrophils to phagocytize bacteria during phage therapy is compensated by the lytic action of the phages.…”

“…Our preliminary observations suggest that phages can influence the phagocyte system: phage therapy transiently decreased both the level of circulating blood neutrophils and the phagocytic index [36]. Phagocytes ingest phages [12]; therefore, phages can affect these cells' metabolic activities.…”

Prophylactic effect of bacteriophages on mice subjected to chemotherapy-induced immunosuppression and bone marrow transplant upon infection with Staphylococcus aureus

“…In addition, the action of phages is selective and not harmful to physiological intestinal microXora. Besides their direct antibacterial actions, phages induce certain bystander eVects beneWcial to the function of the immune system, such as optimization of cytokine production by blood cells isolated from patients [12], acceleration of myelopoiesis [13], and inhibition of both bacteria-and lipopolysaccharide-elicited respiratory burst by human blood phagocytes [14,15]. Phages may also limit metastasis of B16 melanoma in mice, probably by inhibition of cancer cell migration [16,17].…”

Phage therapy: awakening a sleeping giant

“…Nonetheless, certain phages are rapidly cleared from the blood and liver by phagocytes [57,58] or are readily phagocytized by dendritic cells in vitro [59]. In humans, patients who received several weeks of phage therapy for staphylococcal infections, including rhinitis, sinusitis, chronic bronchitis and urinary tract infections, experienced slightly fewer circulating mature neutrophils with a corresponding increase in neutrophil precursors [60]. This suggests that bacterial products released after phage killing are eliciting proinflammatory cytokine responses leading to further recruitment of immature neutrophils [60].…”

“…In humans, patients who received several weeks of phage therapy for staphylococcal infections, including rhinitis, sinusitis, chronic bronchitis and urinary tract infections, experienced slightly fewer circulating mature neutrophils with a corresponding increase in neutrophil precursors [60]. This suggests that bacterial products released after phage killing are eliciting proinflammatory cytokine responses leading to further recruitment of immature neutrophils [60]. Phage preparations have also been shown to modulate immune cell function, such as reduce reactive oxygen species production by phagocytes [61], or promote dendritic cell maturation and IL-12p40 cytokine production [62].…”