Streptococcus pneumoniae anchor to activated human cells by the receptor for platelet-activating factor

DR Cundell, NP Gerard, C Gerard, I Idanpaan-Heikkila… - Nature, 1995 - nature.com
DR Cundell, NP Gerard, C Gerard, I Idanpaan-Heikkila, EI Tuomanen
Nature, 1995nature.com
THE Gram-positive bacterium Streptococcus pneumoniae is a major cause of pneumonia,
sepsis and meningitis1. Although the invasive disease is severe, some 40% of individuals
harbour the pneumococcus in the nasopharynx asymptomatically2. Here we investigate the
molecular elements of the encounter between host and pathogen that distinguish these
different outcomes. We show that inflammatory activation of human cells shifts the targeting
of the pneumococcus to a new receptor, that for the G-protein-coupled platelet-activating …
Abstract
THE Gram-positive bacterium Streptococcus pneumoniae is a major cause of pneumonia, sepsis and meningitis1. Although the invasive disease is severe, some 40% of individuals harbour the pneumococcus in the nasopharynx asymptomatically2. Here we investigate the molecular elements of the encounter between host and pathogen that distinguish these different outcomes. We show that inflammatory activation of human cells shifts the targeting of the pneumococcus 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 phosphoryl-choline to the PAF receptor enhanced adherence, which was coupled to invasion of endothelial, epithelial and PAF-receptor-transfected cells. This progression could be arrested in vitro and in vivo by PAF-receptor-specific antagonists, suggesting a possible approach to therapy.
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