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

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