van Ginkel Frederik W, McGhee Jerry R, Watt James M, Campos-Torres Antonio, Parish Lindsay A, Briles David E
Department of Microbiology, Immunobiology Vaccine Center, University of Alabama at Birmingham, Birmingham, AL 35294-2170, USA.
Proc Natl Acad Sci U S A. 2003 Nov 25;100(24):14363-7. doi: 10.1073/pnas.2235844100. Epub 2003 Nov 10.
Streptococcus pneumoniae cause considerable morbidity and mortality, with persistent neurological sequelae, particularly in young children and the elderly. It is widely assumed that carriage occurs through direct mucosal colonization from the environment whereas meningitis results from invasion from the blood. However, the results of published studies can be interpreted that pneumococci may enter the brain directly from the nasal cavity by axonal transport through olfactory nerves. This hypothesis is based on findings that (i) teichoic acid of the pneumococcal cell wall interact with gangliosides (GLS), (ii) the interaction of GLS with cholera toxin leads to axonal transport through the olfactory nerves into the brain, and (iii) viruses enter the brain through axonal transport into olfactory nerves. After nasal inoculation, we observe high numbers of pneumococci in nasal washes and the olfactory nerves and epithelium. Significant numbers of pneumococci also infected the olfactory bulbs, brain, and the trigeminal ganglia. The absence of bacteremia in this model makes it unlikely that the bacteria entered the brain from the blood stream. Recovery of colony-forming units from the brain, lungs, olfactory nerves, and epithelium and nasal washes was inhibited by incubating pneumococci with GLS before nasal inoculation. These findings, confirmed by PCR and immunohistochemistry, support a GLS-mediated process of infection and are consistent with pneumococci reaching the brain through retrograde axonal transport.
肺炎链球菌会导致相当高的发病率和死亡率，并伴有持续性神经后遗症，尤其是在幼儿和老年人中。人们普遍认为，携带肺炎链球菌是通过环境中的直接黏膜定植，而脑膜炎则是由血液入侵引起的。然而，已发表研究的结果可以解释为，肺炎球菌可能通过嗅觉神经的轴突运输直接从鼻腔进入大脑。这一假设基于以下发现：（i）肺炎球菌细胞壁的磷壁酸与神经节苷脂（GLS）相互作用；（ii）GLS与霍乱毒素的相互作用导致通过嗅觉神经向大脑的轴突运输；（iii）病毒通过轴突运输进入嗅觉神经进而进入大脑。鼻腔接种后，我们在鼻腔灌洗液、嗅觉神经和上皮组织中观察到大量肺炎球菌。大量肺炎球菌还感染了嗅球、大脑和三叉神经节。该模型中不存在菌血症，这使得细菌不太可能从血流进入大脑。在鼻腔接种前将肺炎球菌与GLS一起孵育，可抑制从大脑、肺、嗅觉神经、上皮组织和鼻腔灌洗液中回收菌落形成单位。这些经聚合酶链反应（PCR）和免疫组织化学证实的发现，支持了GLS介导的感染过程，并且与肺炎球菌通过逆行轴突运输到达大脑的情况一致。
