In vivo and in vitro influence of bacteriocins on the functions of innate immune cells

The aim of this study was to investigate the effect of warnerin and hominin, the lantibiotics isolated from the growth media of Staphylococcus warneri and Staphylococcus hominis, respectively as well as action of nisin and the synthetic polyamino acid poly-L-arginine on the functional activity of innate immune cells in vivo and in vitro. The study concerned the following lantibiotics: warnerin (APD ID: AP02801), obtained from the growth medium of Staphylococcus warneri DSM 16081 bacteria, and hominin, isolated from the growth media of Staphylococcus hominis GISK-284 as well as nisin from Lactococcus lactis (Sigma, USA), along with poly-L-arginine hydrochloride, a polycationic synthetic peptide with known antibacterial properties (molecular weight, 5000-15000 Da, Sigma, USA). The In vivo studies were performed using peritoneal cells of white laboratory Swiss mice weighing 20-22 g. Peripheral blood leukocytes from healthy volunteer donors were used as an object of in vitro studies. The absorption activity of peritoneal cavity cells was assessed by flow cytometry, and the production of reactive oxygen species was measured using luminol-dependent chemiluminescence. It was found that both warnerin and hominin did significantly modulate ROS production in vivo. Both peptides enhanced ROS generation by peritoneal macrophages at the entire dose scale, whereas nisin showed a weaker stimulatory effect, increasing ROS production only at a dose of 0.1 mg/ kg. Warnerin in vivo had a statistically significant inhibitory effect on the absorptive activity of peritoneal cells, while hominin and nisin did not affect the percentage of phagocytosis at the entire dose range. In vitro, the production of active oxygen forms was inhibited by warnerin in both spontaneous and stimulated tests at high concentrations, and its stimulatory effect was seen at low concentrations. On the contrary, hominin enhanced the microbicidal potential in unstimulated cultures, but decreased zymosan-induced ROS production; both peptides decreased the scavenging activity of monocytes and neutrophils in vitro. Nisin and poly-L-arginine had no effect on phagocytic activity and microbicidal potential. The obtained data are in line with a hypothesis that antimicrobial peptides inhibit the growth of competitive microflora and exert a modulatory effect on the cell of innate immunity.