title: CCAAT-enhancer binding protein delta (C/EBPδ) protects against Klebsiella pneumoniae-induced pulmonary infection: potential role for macrophage migration.
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.
authors.affiliation: Center for Experimental and Molecular Medicine, University of Amsterdam, Amsterdam, The Netherlands. j.w.duitman@amc.uva.nl
authors.forename: JanWillem
authors.initials: J
authors.lastname: Duitman
authors.forename: Arie J
authors.initials: AJ
authors.lastname: Hoogendijk
authors.forename: Angelique P
authors.initials: AP
authors.lastname: Groot
authors.forename: Roberta R
authors.initials: RR
authors.lastname: Ruela de Sousa
authors.forename: Tom
authors.initials: T
authors.lastname: van der Poll
authors.forename: Sandrine
authors.initials: S
authors.lastname: Florquin
authors.forename: C Arnold
authors.initials: CA
authors.lastname: Spek
mesh_terms: D000818:Animals; D058491:Bacterial Load; D051743:CCAAT-Enhancer-Binding Protein-delta / Q000378:metabolism*; D002465:Cell Movement; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D006801:Humans; D007710:Klebsiella Infections / Q000276:immunology* / Q000473:pathology; D007711:Klebsiella pneumoniae / Q000276:immunology / Q000472:pathogenicity*; D008168:Lung / Q000382:microbiology / Q000473:pathology; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D018410:Pneumonia, Bacterial / Q000276:immunology* / Q000473:pathology; D016019:Survival Analysis
chemical_list: D051743:CCAAT-Enhancer-Binding Protein-delta