Ifn-Gamma(-/-) Mice Resist Actinobacillus Pleuropneumoniae Infection By Promoting Early Lung Il-18 Release And Pmn-I Accumulation

Porcine pleuropneumonia is a common infectious disease of pigs caused by Actinobacillus pleuropneumoniae. Interferon gamma (IFN-gamma) expression increases in the lung of pigs after A. pleuropneumoniae infection, but the role of IFN-gamma during the infection is still obscure. In this study, an IFN-gamma(-/-) mouse infection model was established, and bacterial load, levels of inflammatory cytokines, and types of neutrophils in the lungs were studied at different times post-A. pleuropneumoniae infection. We found that wild-type (WT) mice were more susceptible to A. pleuropneumoniae than IFN-gamma(-/-) mice. At 6 h postinfection (hpi), the expression of interleukin 18 (IL-18) and IL-1 beta in the lungs of IFN-gamma(-/-) mice was significantly increased compared to WT mice. The bacterial load and levels of inflammatory cytokines (IL-1 beta and IL-6) of IFN-gamma(-/-) mice were significantly reduced at 12 hpi compared to WT mice. After an initial loss, the numbers of lung polymorphonuclear (PMN)-I cells dramatically increased in the lungs of IFN-gamma(-/-) but not WT mice, whereas PMN-II cells continually decreased. Finally, in vivo administration of IL-18 significantly reduced clinical scores and bacterial load in the lungs of A. pleuropneumoniae-infected mice. This study identifies IFN-gamma as a target for regulating the inflammatory response in the lung and provides a basis for understanding the course of clinical bacterial pneumonia and for the formulation of treatment protocols.