title: CCAAT/enhancer-binding protein δ facilitates bacterial dissemination during pneumococcal pneumonia in a platelet-activating factor receptor-dependent manner.
abstract: CCAAT/enhancer-binding protein δ (C/EBPδ) recently emerged as an essential player in the inflammatory response to bacterial infections. C/EBPδ levels increase rapidly after a proinflammatory stimulus, and increasing C/EBPδ levels seem to be indispensable for amplification of the inflammatory response. Here we aimed to elucidate the role of C/EBPδ in host defense in community-acquired pneumococcal pneumonia. We show that C/EBPδ(-/-) mice are relatively resistant to pneumococcal pneumonia, as indicated by delayed and reduced mortality, diminished outgrowth of pneumococci in lungs, and reduced dissemination of the infection. Moreover, expression of platelet-activating factor receptor (PAFR), which is known to potentiate bacterial translocation of gram-positive bacteria, was significantly reduced during infection in C/EBPδ(-/-) mice compared with WT controls. Importantly, cell stimulation experiments revealed that C/EBPδ potentiates PAFR expression induced by lipoteichoic acid and pneumococci. Thus, C/EBPδ exaggerates bacterial dissemination during Streptococcus pneumoniae-induced pulmonary infection, suggesting an important role for PAFR-dependent bacterial translocation.
authors.affiliation: Academic Medical Center, 1105 AZ Amsterdam, The Netherlands. j.w.duitman@amc.uva.nl
authors.forename: Janwillem
authors.initials: J
authors.lastname: Duitman
authors.forename: Marcel
authors.initials: M
authors.lastname: Schouten
authors.forename: Angelique P
authors.initials: AP
authors.lastname: Groot
authors.forename: Keren S
authors.initials: KS
authors.lastname: Borensztajn
authors.forename: Joost B
authors.initials: JB
authors.lastname: Daalhuisen
authors.forename: Sandrine
authors.initials: S
authors.lastname: Florquin
authors.forename: Tom
authors.initials: T
authors.lastname: van der Poll
authors.forename: C Arnold
authors.initials: CA
authors.lastname: Spek
mesh_terms: D000818:Animals; D015153:Blotting, Western; D051743:CCAAT-Enhancer-Binding Protein-delta / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation / Q000502:physiology*; D006652:Histological Techniques; D006801:Humans; D008156:Luciferases; D008168:Lung / Q000382:microbiology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D010539:Permeability; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism*; D011018:Pneumonia, Pneumococcal / Q000276:immunology* / Q000382:microbiology; D060888:Real-Time Polymerase Chain Reaction; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D018709:Statistics, Nonparametric
chemical_list: D010980:Platelet Membrane Glycoproteins; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; D051743:CCAAT-Enhancer-Binding Protein-delta; D008156:Luciferases