CCAAT-Enhancer Binding Protein Delta (C/EBP delta) Protects Against Klebsiella pneumoniae-Induced Pulmonary Infection: Potential Role for Macrophage Migration

Mounting evidence suggests an important role for CCAAT-enhancer binding protein delta (C/EBPd) in the acute-phase response after bacterial infection. However, whether C/EBPd limits pneumonia remains elusive and is the aim of this study. Therefore, bacterial outgrowth, inflammatory responses, inflammatory cell influx, and survival were assessed in wild-type and C/EBP delta(-/-) mice infected with Klebsiella pneumoniae via the airways. We showed that C/EBP delta expression is highly induced in the lung during pulmonary infection and that Klebsiella-induced mortality was significantly increased among C/EBP delta(-/-) mice. Bacterial loads and inflammatory responses were similar in wild-type and C/EBP delta(-/-) mice early during infection, whereas bacterial loads were increased in C/EBP delta(-/-) mice later during infection. Moreover, macrophage numbers were reduced in lungs of C/EBP delta(-/-) mice. In vitro experiments showed that C/EBP delta only slightly affects macrophage function. Our data thus show that C/EBP delta contributes to host defense against Klebsiella-induced pneumonia and suggests that C/EBP delta-dependent macrophage mobilization is a key mechanism