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JanWillem Duitman, Arie J. Hoogendijk, Angelique P. Groot, Roberta R. Ruela de Sousa, Tom van der Poll, Sandrine Florquin, C. Arnold Spek, CCAAT-Enhancer Binding Protein Delta (C/EBPδ) Protects Against Klebsiella pneumoniae–Induced Pulmonary Infection: Potential Role for Macrophage Migration, The Journal of Infectious Diseases, Volume 206, Issue 12, 15 December 2012, Pages 1826–1835, https://doi.org/10.1093/infdis/jis615
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Abstract
Mounting evidence suggests an important role for CCAAT-enhancer binding protein delta (C/EBPδ) in the acute-phase response after bacterial infection. However, whether C/EBPδ 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/EBPδ−/− mice infected with Klebsiella pneumoniae via the airways. We showed that C/EBPδ expression is highly induced in the lung during pulmonary infection and that Klebsiella-induced mortality was significantly increased among C/EBPδ−/− mice. Bacterial loads and inflammatory responses were similar in wild-type and C/EBPδ−/− mice early during infection, whereas bacterial loads were increased in C/EBPδ−/− mice later during infection. Moreover, macrophage numbers were reduced in lungs of C/EBPδ−/− mice. In vitro experiments showed that C/EBPδ only slightly affects macrophage function. Our data thus show that C/EBPδ contributes to host defense against Klebsiella-induced pneumonia and suggests that C/EBPδ-dependent macrophage mobilization is a key mechanism.