How Does Streptococcus pneumoniae Invade the Brain?

Streptococcus pneumoniae (the pneumococcus) is the major cause of bacterial meningitis. The mechanisms by which pneumococci from the bloodstream penetrate the blood–brain barrier to reach the brain are not fully understood. Receptor-mediated adhesion of the bacteria to the brain endothelium is considered a key event leading to meningitis development. The aim of this review is to discuss recent advances and perspectives related to the interactions of S. pneumoniae with the blood–brain barrier during the events leading to meningitis. Altogether, the available data suggest that, by precisely defining the pathways and ligands by which S. pneumoniae adheres to specific receptors, it may be possible to interfere with the respective mechanisms and develop strategies to prevent or even cure pneumococcal meningitis.

TrendsStreptococcus pneumoniae, the main causative agent of bacterial meningitis, penetrates the blood–brain barrier by binding to PECAM-1 and pIgR expressed by brain vascular endothelial cells.Overall, recent findings suggest that PECAM-1 and pIgR, together with platelet-activating factor receptor (PAFR), another receptor thought to be more involved in signaling rather than physical binding, might cooperate during adhesion of pneumococci to brain endothelial cells.The passage of S. pneumoniae across the blood–brain barrier is a crucial step for meningitis development. The knowledge of how S. pneumoniae penetrates the blood–brain barrier can be used to develop strategies aimed at interfering with the respective pathways in order to prevent the entry of the pathogen into the brain.