Human neutrophil response to Pseudomonas bacteriophages

Abstract

The immune system offers several mechanisms of response to remove harmful microbes that invade the human body. As a first line of defense, neutrophils can remove pathogens by phagocytosis, inactivate them by the release of reactive oxygen species (ROS) or immobilize them by neutrophil extracellular traps (NETs). Although, recent studies have shown that bacteriophages (phages) make up a large portion of human microbiomes and are currently being explored as human antibacterial therapeutics, neutrophilic responses to phages are still elusive. Here, we show that exposure of isolated human resting neutrophils to high concentration of thePseudomonasphage PAK_P1 led to a 2.8 fold increase in interleukin-8 (IL-8) secretion. Importantly, phage exposure did not further affect resting neutrophil apoptosis or induce necrosis, CD11 expression, oxidative burst, and NETs. Similarly, inflammatory stimuli activated neutrophil effector responses were unaffected by phage exposure. Our work suggest that phages are unlikely to inadvertently cause excessive neutrophil responses that could damage tissues and worsen disease. Because IL-8 functions as a chemoattractant directing immune cells to sites of infection and inflammation, phage-stimulated IL-8 production may boost host immune responses.

Interactions of Bacteriophages with Animal and Human Organisms—Safety Issues in the Light of Phage Therapy

“…They showed that the application of bacteriophage at a high concentration of 10 9 /mL induced IL-8 production. However, no induction of apoptosis of resting neutrophils was observed, nor did it induce expression of the surface CD11b protein or lead to an oxidative burst [65]. These results were similar to those obtained by Borysowski et al [66,67], who showed that the exposure of bacteriophage A3/r to neutrophils did not lead to an oxygen burst and did not cause neutrophil degranulation.…”

“…A recent study Roach et al [65] examined the effect of bacteriophage PAK_P1 on the response of human neutrophils. They showed that the application of bacteriophage at a high concentration of 10 9 /mL induced IL-8 production.…”