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CCAAT/enhancer-binding protein ? facilitates bacterial dissemination during pneumococcal pneumonia in a platelet-activating factor receptor-dependent manner.


ABSTRACT: CCAAT/enhancer-binding protein ? (C/EBP?) recently emerged as an essential player in the inflammatory response to bacterial infections. C/EBP? levels increase rapidly after a proinflammatory stimulus, and increasing C/EBP? levels seem to be indispensable for amplification of the inflammatory response. Here we aimed to elucidate the role of C/EBP? in host defense in community-acquired pneumococcal pneumonia. We show that C/EBP?(-/-) 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/EBP?(-/-) mice compared with WT controls. Importantly, cell stimulation experiments revealed that C/EBP? potentiates PAFR expression induced by lipoteichoic acid and pneumococci. Thus, C/EBP? exaggerates bacterial dissemination during Streptococcus pneumoniae-induced pulmonary infection, suggesting an important role for PAFR-dependent bacterial translocation.

SUBMITTER: Duitman J 

PROVIDER: S-EPMC3384171 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature

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CCAAT/enhancer-binding protein δ facilitates bacterial dissemination during pneumococcal pneumonia in a platelet-activating factor receptor-dependent manner.

Duitman Janwillem J   Schouten Marcel M   Groot Angelique P AP   Borensztajn Keren S KS   Daalhuisen Joost B JB   Florquin Sandrine S   van der Poll Tom T   Spek C Arnold CA  

Proceedings of the National Academy of Sciences of the United States of America 20120521 23


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 indi  ...[more]

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