STREPTOCOCCUS-PNEUMONIAE ANCHOR TO ACTIVATED HUMAN-CELLS BY THE RECEPTOR FOR PLATELET-ACTIVATING-FACTOR

THE Gram-positive bacterium Streptococcus pneumoniae is a major cause of pneumonia, sepsis and meningitis(1). Although the invasive disease is severe, some 40% of individuals harbour the pneumococcus in the nas opharynx asymptomatically(2). Here we investigate the molecular elemen ts of the encounter between host and pathogen that distinguish these d ifferent outcomes. We show that inflammatory activation of human cells shifts the targeting of the pneumococcos to a new receptor, that for the G-protein-coupled platelet-activating factor (PAF). Only virulent pneumococci engage the PAF receptor. Attachment of the bacterial phosp horylcholine to the PAF receptor enhanced adherence, which was coupled to invasion of endothelial, epithelial and PAF-receptor-transfected c ells. This progression could be arrested in vitro and in vivo by PAF-r eceptor-specific antagonists, suggesting a possible approach to therap y.