Cundell D R, Gerard N P, Gerard C, Idanpaan-Heikkila I, Tuomanen E I
Laboratory of Molecular Infectious Diseases, Rockefeller University, New York, New York 10021-6399, USA.
Nature. 1995 Oct 5;377(6548):435-8. doi: 10.1038/377435a0.
The Gram-positive bacterium Streptococcus pneumoniae is a major cause of pneumonia, sepsis and meningitis. Although the invasive disease is severe, some 40% of individuals harbour the pneumococcus in the nasopharynx asymptomatically. 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 phosphorylcholine 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.
革兰氏阳性菌肺炎链球菌是肺炎、败血症和脑膜炎的主要病因。尽管侵袭性疾病很严重，但约40%的个体在鼻咽部无症状地携带肺炎球菌。在这里，我们研究了宿主与病原体之间相互作用的分子因素，这些因素区分了这些不同的结果。我们发现，人类细胞的炎症激活将肺炎球菌的靶向转移到一种新的受体，即G蛋白偶联的血小板活化因子（PAF）受体。只有有毒力的肺炎球菌才能与PAF受体结合。细菌磷酸胆碱与PAF受体的结合增强了黏附，这与内皮细胞、上皮细胞和PAF受体转染细胞的侵袭有关。这种进展在体外和体内都可以被PAF受体特异性拮抗剂阻止，这提示了一种可能的治疗方法。
