Detrimental role for CCAAT/enhancer binding protein δ in blood-borne brain infection.
BACKGROUND
The most frequent pathogen that causes bacterial meningitis is the Gram-positive bacterium Streptococcus (S.) pneumoniae. CCAAT/enhancer binding protein δ is a transcription factor that has recently been hypothesized to play a detrimental role in outcome of meningitis caused by S. pneumoniae. Here, we studied the role of C/EBPδ prior to the development of pneumococcal meningitis.


METHODS
Wild-type and C/EBPδ-deficient mice (C/EBPδ-/-) were intraveneously infected with S. pneumoniae and sacrificed after 24 or 48 h. cebpδ expression, bacterial loads, inflammatory response and pathology in the brain were assessed.


RESULTS
S. pneumoniae induces cebpδ expression in the brain during blood-borne brain infection. In comparison to wild-type mice, C/EBPδ-/-animals showed decreased bacterial loads in blood and brain 48 h after inoculation. In the blood compartment, the host inflammatory response was significantly lower upon infection in C/EBPδ-/-mice as compared to wild-type mice.


CONCLUSIONS
C/EBPδ facilitates bacterial dissemination to the brain and enhances the immune response in the blood compartment. Our study suggests that C/EBPδ plays a detrimental role during the initial development of blood-borne brain infection.
Center for Experimental and Molecular Medicine (CEMM) Academic Medical Center, University of Amsterdam, P.O. Box 22660, 1100DD, Amsterdam, The Netherlands. j.w.duitman@amc.uva.nl.
JanWillem
J
Duitman
Department of Neurology, Academic Medical Center, 1100DD, Amsterdam, The Netherlands.|Neuroinfection and Inflammation, Amsterdam Neuroscience, Amsterdam, The Netherlands.
Mercedes
M
Valls Serón
Department of Neurology, Academic Medical Center, 1100DD, Amsterdam, The Netherlands.|Neuroinfection and Inflammation, Amsterdam Neuroscience, Amsterdam, The Netherlands.
JooYeon
J
Engelen-Lee
Department of Neurology, Academic Medical Center, 1100DD, Amsterdam, The Netherlands.|Neuroinfection and Inflammation, Amsterdam Neuroscience, Amsterdam, The Netherlands.
Matthijs C
MC
Brouwer
Center for Experimental and Molecular Medicine (CEMM) Academic Medical Center, University of Amsterdam, P.O. Box 22660, 1100DD, Amsterdam, The Netherlands.
C Arnold
CA
Spek
Department of Neurology, Academic Medical Center, 1100DD, Amsterdam, The Netherlands.|Neuroinfection and Inflammation, Amsterdam Neuroscience, Amsterdam, The Netherlands.
Diederik
D
van de Beek
D000818:Animals; D058491:Bacterial Load; D001921:Brain / Q000382:microbiology; D051743:CCAAT-Enhancer-Binding Protein-delta / Q000378:metabolism*; D006801:Humans; D008586:Meningitis, Pneumococcal / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D013296:Streptococcus pneumoniae; D014157:Transcription Factors
D014157:Transcription Factors; D051743:CCAAT-Enhancer-Binding Protein-delta
Blood-borne brain infection; C/EBPδ; CAAT/enhancer-binding protein δ; Experimental meningitis; Streptococcus pneumoniae