IFN-?-/-mice Defensed Actinobacillus Pleuropneumoniae Infection Through Promoting Lung PMN-? Accumulation And IL-18 Release During Early Stage

Actinobacillus pleuropneumoniae(APP)is an important pathogen causing infectious pleural pneumonia in piglets.The expression of IFN-y increased significantly in lung tissues of pigs with pleural pneumonia.In order to understand the role of IFN-y in APP infection,this study explored the mechanism of defensing APP in IFN-?-/-mice from the aspects of neutrophils and inflammatory cytokines Clinical scores and pulmonary bacterial load of IFN-?-/-mice were compared with wild-type mice at 6 h,12 h and 24 h after APP infection.The expression of pulmonary inflammatory cytokines and neutrophil chemokines were detected by qPCR and ELISA.And the subtype and death of pulmonary neutrophils were detected by flow cytometry.The results showed that the survival rate of IFN-?-/-mice after APP infection was significantly increased than wild-type mice.Further study found that compared with wild-type mice,the ability of bacteria clearance increased in IFN-?-/-mice(p<0.01).And the pulmonary congestion and edema alleviated in IFN-?-/-mice.The expression of inflammatory cytokines IL-18,IL-1?,TNF-? and neutrophils chemokines CXCL1,CXCL2 and CXCL5 increased at 6 h after infection(p<0.01)and decreased at 12 h(p<0.01).The ration of neutrophils in the IFN-?-/-mice lung was significantly decreased(p<0.01),but there was no significant change in necrosis and apoptosis of neutrophils(p>0.05).Compared with WT mice,the expression of PMN-?(CD49+CD11b-)increased in IFN-?-/-mice,and declined slowly during early stage and increased in last stage afte APP infection.The expression of PMN-?(CD49-CD11b+)significantly reduced in IFN-?-/-mice.To further explore the role of IL-18 in pneumonia,it was found that after intraperitoneal injection of IL-18,pulmonary bacterial loda decreased(p<0.05),also the clinical symptoms and lung lesions relieved.PMN-? accumulation increased after IL-18 treatment(p<0.05).IL-18 could promote the release of neutrophil extracellular traps and the expression of inflammatory cytokines,but had no significant effect on neutrophil phagocytosis and degranulation(p>0.05).In summary,these results suggest that IFN-? deletion can promote the secretion of IL-18 in lung,enhance PMN-? chemotaxis,inhibit PMN-? polarization,induce the early acute inflammatory response,enhance the ability of neutrophils to clear the bacteria.And it can enhance the survival rate of mice after APP infection.This study provides a basis for the monitoring of the course of clinical bacterial pneumonia and the formulation of a phased and refined treatment regimen.IFN-y may be a target for regulating inflammatory response in lung tissue.