The Effect Of IL-33 Regulating Neutrophil To Staphylococcus Aureus Infection

Staphylococcus(S.) aureus is one of the most common pyogenic cocci, which is the major pathogenic bacterium of nosocomial infection in the world. In recent years, due to the abuse of antibiotics, S. aureus obtained drug resistance to multiple antibiotics, and its pathogenicity was constantly increasing with the increased mortality rate. Neutrophils are the important component of innate immune cells in the body against invading microbes,especially the first line of suppurative bacterial infection. IL-33 has recently been found to exhibit a large body of biological activities, which plays an essential role in infectious diseases, cardiovascular diseases and autoimmune diseases. In this article, we will establish the animal model of methicillin-resistant S. aureus(MRSA) infection in mice, and study the therapeutic effect and immunological mechanism of IL-33 in this model for providing the new evidence for the clinical treatment of MRSA infection.ObjectiveWe observe the effect of IL-33 in two kinds of infection mice models, and explore the potential immunological mechanism in anti-infection immunity. At the same time, the effect of IL-33 on neutrophil bactericidal activity may be also elucidated in vitro. Altogether, this study will provide evidence for the prevention and therapy of MRSA infection.MethodsTo establish two models of peritoneal and cutaneous MRSA infection in mice, we observe the effect of IL-33 on mice survival rate and wound healing time in these animals,respectively. Load of bacteria in different organs, neutrophil in blood and peritoneal fluid,and proinflammatory cytokines were measured in abdomen-infected mice. Local wound neovascularization, granulation tissue production, load of bacteria and the NETs productionwere checked in skin-infected mice. Flow cytometry and immunofluorescent staining were used to detect the bactericidal mechanism of IL-33-regulating neutrophils in bacterial infection.Results1. Protective effect of IL-33 on MRSA abdominal infectionAfter treatment of mice abdominal infection by IL-33, food intake of mice was significantly improved and reaction was sensitive. The survival rate of mice significantly increased. The number of white blood cells in peripheral blood and peritoneal fluid were increased. Bacterial load in peripheral blood, peritoneal fluid and organs were reduced. At the same time, inflammatory cytokines IL-6、IL-17 A and TNF-α levels were increased.2. Protective effect of IL-33 on MRSA skin infectionAfter treatment of mice skin infection by IL-33, the healing time of mice was 14 days shorten than the control group. The bacterial load in the IL-33-treated group was decreased compared with the control group. The formation of Neutrophil extracellular traps(NETs)on the abscess parts were increased in the IL-33-treated group.3. Effect of IL-33 on neutrophil bactericidal mechanismNeutrophil chemotaxis, phagocytosis and cytotoxicity were increased in the IL-33-pretreated group. The activity of neutrophil respiratory burst and the expression of adhesion molecules were increased the IL-33-pretreated group. Meantime, the PI3K/AKT/m TOR signaling pathway was activated and the generation of NETs was also increased in IL-33-pretreated mice.ConclusionIL-33 regulates neutrophil biological activity through multiple channels, and enhances the immune function of neutrophils in anti-MRSA infection.