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

CCAAT/enhancer-binding protein ô (C/EBP5) recently emerged as an essential player in the inflammatory response to bacterial infections. C/EBP8 levels increase rapidly after a proinflammatory stimulus, and increasing C/EBP5 levels seem to be indispensable for amplification of the inflammatory response. Here we aimed to elucidate the role of C/EBP6 in host defense in community-acquired pneumococcal pneumonia. We show that C/EBPô∼'∼ 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/EBPô∼'∼ mice compared with WT controls. Importantly, cell stimulation experiments revealed that C/EBP6 potentiates PAFR expression induced by lipoteichoic acid and pneumococci. Thus, C/EBP8 exaggerates bacterial dissemination during Streptococcus pneumon/ae-induced pulmonary infection, suggesting an important role for PAFR-dependent bacterial translocation. [ABSTRACT FROM AUTHOR]