title: CCAAT/enhancer-binding protein δ (C/EBPδ) aggravates inflammation and bacterial dissemination during pneumococcal meningitis.
abstract: BACKGROUND
  The prognosis of bacterial meningitis largely depends on the severity of the inflammatory response. The transcription factor CAAT/enhancer-binding protein δ (C/EBPδ) plays a key role in the regulation of the inflammatory response during bacterial infections. Consequently, we assessed the role of C/EBPδ during experimental meningitis.
  
  
  METHODS
  Wild-type and C/EBPδ-deficient mice (C/EBPδ(-/-)) were intracisternally infected with Streptococcus pneumoniae and sacrificed after 6 or 30 h, or followed in a survival study.
  
  
  RESULTS
  In comparison to wild-type mice, C/EBPδ(-/-) mice showed decreased bacterial loads at the primary site of infection and decreased bacterial dissemination to lung and spleen 30 h after inoculation. Expression levels of the inflammatory mediators IL-10 and KC were lower in C/EBPδ(-/-) brain homogenates, whereas IL-6, TNF-α, IL-1β, and MIP-2 levels were not significantly different between the two genotypes. Moreover, C/EBPδ(-/-) mice demonstrated an attenuated systemic response as reflected by lower IL-10, IL-6, KC, and MIP-2 plasma levels. No differences in clinical symptoms or in survival were observed between wild-type and C/EBPδ(-/-) mice.
  
  
  CONCLUSIONS
  C/EBPδ in the brain drives the inflammatory response and contributes to bacterial dissemination during pneumococcal meningitis. C/EBPδ does, however, not affect clinical parameters of the disease and does not confer a survival benefit.
authors.affiliation: Department of Neurology, Center of Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Meibergdreef 9, PO Box 22660, 1100DD, Amsterdam, The Netherlands. m.vallsseron@amc.uva.nl.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Valls Serón
authors.affiliation: Center for Experimental and Molecular Medicine (CEMM), Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. j.w.duitman@amc.uva.nl.
authors.forename: JanWillem
authors.initials: J
authors.lastname: Duitman
authors.affiliation: Department of Neurology, Center of Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Meibergdreef 9, PO Box 22660, 1100DD, Amsterdam, The Netherlands. m.geldhoff@amc.uva.nl.
authors.forename: Madelijn
authors.initials: M
authors.lastname: Geldhoff
authors.affiliation: Department of Neurology, Center of Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Meibergdreef 9, PO Box 22660, 1100DD, Amsterdam, The Netherlands. j.y.lee@amc.uva.nl.
authors.forename: JooYeon
authors.initials: J
authors.lastname: Engelen-Lee
authors.affiliation: Department of Neurology, Center of Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Meibergdreef 9, PO Box 22660, 1100DD, Amsterdam, The Netherlands. s.r.havik@amc.uva.nl.
authors.forename: Stefan R
authors.initials: SR
authors.lastname: Havik
authors.affiliation: Department of Neurology, Center of Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Meibergdreef 9, PO Box 22660, 1100DD, Amsterdam, The Netherlands. m.c.brouwe@amc.uva.nl.
authors.forename: Matthijs C
authors.initials: MC
authors.lastname: Brouwer
authors.affiliation: Department of Neurology, Center of Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Meibergdreef 9, PO Box 22660, 1100DD, Amsterdam, The Netherlands. d.vandebeek@amc.uva.nl.
authors.forename: Diederik
authors.initials: D
authors.lastname: van de Beek
authors.affiliation: Center for Experimental and Molecular Medicine (CEMM), Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. c.a.spek@amc.uva.nl.
authors.forename: C Arnold
authors.initials: CA
authors.lastname: Spek
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D058491:Bacterial Load; D051743:CCAAT-Enhancer-Binding Protein-delta / Q000235:genetics / Q000378:metabolism*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D018450:Disease Progression; D015964:Gene Expression Regulation, Bacterial / Q000235:genetics*; D007249:Inflammation / Q000209:etiology*; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008586:Meningitis, Pneumococcal / Q000150:complications*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000378:metabolism; D013296:Streptococcus pneumoniae / Q000502:physiology*; D013997:Time Factors
chemical_list: D016207:Cytokines; D012333:RNA, Messenger; D051743:CCAAT-Enhancer-Binding Protein-delta; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase