Koppel Estella A, Saeland Eirikur, de Cooker Désirée J M, van Kooyk Yvette, Geijtenbeek Teunis B H
Department of Molecular Cell Biology & Immunology, VU University Medical Center Amsterdam, v.d. Boechorststraat 7, 1081 BT Amsterdam, The Netherlands.
Immunobiology. 2005;210(2-4):203-10. doi: 10.1016/j.imbio.2005.05.014.
The Gram-positive bacterium Streptococcus pneumoniae is the leading causative pathogen in community-acquired pneumonia. The ever-increasing frequency of antibiotic-resistant S. pneumoniae strains severely hampers effective treatments. Thus, a better understanding of the mechanisms involved in the pathogenesis of pneumococcal disease is needed; in particular, of the initial interactions that take place between the host and the bacterium. Recognition of pathogens by dendritic cells is one of the most crucial steps in the induction of an immune response. For efficient pathogen recognition, dendritic cells express various kinds of receptors, including the DC-specific C-type lectin DC-SIGN. Pathogens such as Mycobacterium tuberculosis and HIV target DC-SIGN to escape immunity. Here the in vitro binding of DC-SIGN with S. pneumoniae was investigated. DC-SIGN specifically interacts with S. pneumoniae serotype 3 and 14 in contrast to other serotypes such as 19F. While the data described here suggest that DC-SIGN interacts with S. pneumoniae serotype 14 through a ligand expressed by the capsular polysaccharide, the binding to S. pneumoniae serotype 3 appears to depend on an as yet unidentified ligand. Despite the binding capacity of the capsular polysaccharide of S. pneumoniae 14 to DC-SIGN, no immunomodulatory effects on the dendritic cells were observed. The immunological consequences of the serotype-specific capacity to interact with DC-SIGN should be further explored and might result in new insights in the development of new and more potent vaccines.
革兰氏阳性菌肺炎链球菌是社区获得性肺炎的主要致病病原体。抗生素耐药性肺炎链球菌菌株的频率不断增加,严重阻碍了有效治疗。因此,需要更好地了解肺炎球菌疾病发病机制中涉及的机制;特别是宿主与细菌之间发生的初始相互作用。树突状细胞对病原体的识别是诱导免疫反应中最关键的步骤之一。为了有效识别病原体,树突状细胞表达各种受体,包括DC特异性C型凝集素DC-SIGN。结核分枝杆菌和HIV等病原体靶向DC-SIGN以逃避免疫。在此研究了DC-SIGN与肺炎链球菌的体外结合。与其他血清型如19F相比,DC-SIGN与肺炎链球菌血清型3和14特异性相互作用。虽然这里描述的数据表明DC-SIGN通过荚膜多糖表达的配体与肺炎链球菌血清型14相互作用,但与肺炎链球菌血清型3的结合似乎取决于一种尚未确定的配体。尽管肺炎链球菌14的荚膜多糖具有与DC-SIGN结合的能力,但未观察到对树突状细胞的免疫调节作用。血清型特异性与DC-SIGN相互作用的免疫后果应进一步探索,这可能会为新型更有效疫苗的开发带来新的见解。