title: Platelet endothelial cell adhesion molecule-1, a putative receptor for the adhesion of Streptococcus pneumoniae to the vascular endothelium of the blood-brain barrier.
abstract: The Gram-positive bacterium Streptococcus pneumoniae is the main causative agent of bacterial meningitis. S. pneumoniae is thought to invade the central nervous system via the bloodstream by crossing the vascular endothelium of the blood-brain barrier. The exact mechanism by which pneumococci cross endothelial cell barriers before meningitis develops is unknown. Here, we investigated the role of PECAM-1/CD31, one of the major endothelial cell adhesion molecules, in S. pneumoniae adhesion to vascular endothelium of the blood-brain barrier. Mice were intravenously infected with pneumococci and sacrificed at various time points to represent stages preceding meningitis. Immunofluorescent analysis of brain tissue of infected mice showed that pneumococci colocalized with PECAM-1. In human brain microvascular endothelial cells (HBMEC) incubated with S. pneumoniae, we observed a clear colocalization between PECAM-1 and pneumococci. Blocking of PECAM-1 reduced the adhesion of S. pneumoniae to endothelial cells in vitro, implying that PECAM-1 is involved in pneumococcal adhesion to the cells. Furthermore, using endothelial cell protein lysates, we demonstrated that S. pneumoniae physically binds to PECAM-1. Moreover, both in vitro and in vivo PECAM-1 colocalizes with the S. pneumoniae adhesion receptor pIgR. Lastly, immunoprecipitation experiments revealed that PECAM-1 can physically interact with pIgR. In summary, we show for the first time that blood-borne S. pneumoniae colocalizes with PECAM-1 expressed by brain microvascular endothelium and that, in addition, they colocalize with pIgR. We hypothesize that this interaction plays a role in pneumococcal binding to the blood-brain barrier vasculature prior to invasion into the brain.
authors.affiliation: Department of Medical Microbiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Federico
authors.initials: F
authors.lastname: Iovino
authors.affiliation: Department of Pathology & Medical Biology, Medical Biology Section, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Grietje
authors.initials: G
authors.lastname: Molema
authors.affiliation: Department of Medical Microbiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands bijlsmajje@gmail.com.
authors.forename: Jetta J E
authors.initials: JJ
authors.lastname: Bijlsma
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism* / Q000382:microbiology; D002460:Cell Line; D042783:Endothelial Cells / Q000378:metabolism* / Q000382:microbiology; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000382:microbiology; D006801:Humans; D016920:Meningitis, Bacterial / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism*; D013296:Streptococcus pneumoniae / Q000378:metabolism*
chemical_list: D019408:Platelet Endothelial Cell Adhesion Molecule-1