Zinc oxide nanoparticles (ZnONPs) are inorganic nano-biomaterials with excellent antimicrobial properties. However, their effects on the anti-infection ability of the innate immune system remains poorly understood. The aim of the present study was to explore the potential immunomodulatory effects of ZnONPs on the innate immune system, represented by polymorphonuclear leukocytes (PMNs), and determine whether they can act synergistically to resist pathogen infections. In vitro experiment showed that ZnONPs not only exhibit obvious antibacterial activity at biocompatible concentrations but also enhance the antibacterial property of PMNs. In vivo experiments demonstrated the antibacterial effect of ZnONPs, accompanied by more infiltration of subcutaneous immune cells. Further ex vivo and in vitro experiments revealed that ZnONPs enhanced the migration of PMNs, promoted their bacterial phagocytosis efficiency, proinflammatory cytokine (TNF-α, IL-1β, and IL-6) expression, and reactive oxygen species (ROS) production. In summary, this study revealed potential synergistic effects of ZnONPs on PMNs to resist pathogen infection and the underlying mechanisms. The findings suggest that attempts should be made to fabricate and apply biomaterials in order to maximize their synergy with the innate immune system, thus promoting the host's resistance to pathogen invasion.
Keywords: antimicrobial property; polymorphonuclear leukocyte; synergistic effect; zinc oxide nanoparticle.