IFN-γ-/- 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 (APP). IFN-γ expression increases in the lung of pigs after APP infection, but the role of IFN-γ during the infection is still obscure. In this study, an IFN-γ-/- mouse infection model was established, and bacterial load, the levels of inflammatory cytokines and the types of neutrophils in the lungs were studied at different times post APP infection. We found that wild-type (WT) mice were more susceptible to APP than IFN-γ-/- mice. At 6 h post infection (hpi), the expression of IL-18 and IL-1β in the lungs of IFN-γ-/- mice were significantly increased compared to WT mice. The bacterial load and levels of inflammatory cytokines (IL-1β and IL-6) of IFN-γ-/- 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-γ-/- 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 APP-infected mice. This study identifies IFN-γ 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.