Park Jin-Yeon, Choi Heong-Jwa, Prabagar Miglena G V, Choi Woo-Sung, Kim Sun-Jong, Cheong Cheolho, Park Chae Gyu, Chin Chan Young, Kang Young-Sun
Department of Biomedical Science & Technology, Institute of Biomedical Science & Technology (IBST), Konkuk University, 1 Hwayang-dong, Kwangjin-gu, Seoul 143-701, Republic of Korea.
Neurosci Lett. 2009 Feb 6;450(3):246-51. doi: 10.1016/j.neulet.2008.11.070. Epub 2008 Dec 10.
Although Streptococcus pneumoniae is the major cause of meningitis, how it causes disease is poorly understood. The C-type lectin SIGN-R1 mediates the recently described SIGN-R1 complement activation pathway, which operates against capsular polysaccharides (CPSs) of S. pneumoniae in splenic marginal macrophages. Here, we demonstrate that SIGN-R1, as well as the rat SIGN-R1 homologue CD209b are expressed in most regions of mouse or rat brain, respectively. Moreover, both C-type lectins are obviously expressed on microglia, but not on neurons or astrocytes. We also found that rat CD209b mediates the uptake of dextran or CPS14 within the rat splenic marginal zone, similar to SIGN-R1. On microglia, rat CD209b also mediates the uptake of CPS14 of S. pneumoniae. Our findings strongly suggest that both rat CD209b and SIGN-R1 on microglia mediate the SIGN-R1 complement activation pathway against S. pneumoniae, and thereby plays an important role in the pathogenesis of pneumococcal meningitis.
尽管肺炎链球菌是脑膜炎的主要病因,但其致病机制仍知之甚少。C型凝集素SIGN-R1介导了最近描述的SIGN-R1补体激活途径,该途径在脾边缘巨噬细胞中对抗肺炎链球菌的荚膜多糖(CPS)发挥作用。在此,我们证明SIGN-R1以及大鼠SIGN-R1同源物CD209b分别在小鼠或大鼠大脑的大多数区域表达。此外,这两种C型凝集素均明显表达于小胶质细胞上,而在神经元或星形胶质细胞上不表达。我们还发现,大鼠CD209b介导大鼠脾边缘区内右旋糖酐或CPS14的摄取,类似于SIGN-R1。在小胶质细胞上,大鼠CD209b也介导肺炎链球菌CPS14的摄取。我们的研究结果有力地表明,小胶质细胞上的大鼠CD209b和SIGN-R1均介导针对肺炎链球菌的SIGN-R1补体激活途径,从而在肺炎球菌性脑膜炎的发病机制中发挥重要作用。