Platelet endothelial cell adhesion molecule-1 (PECAM-1), a putative receptor for the adhesion of Streptococcus pneumoniae to the vascular endothelium of the blood-brain barrier.

Infect Immun. 2014 Jun 9. pii: IAI.00046-14. [Epub ahead of print]

Platelet endothelial cell adhesion molecule-1 (PECAM-1), a putative receptor for the adhesion of Streptococcus pneumoniae to the vascular endothelium of the blood-brain barrier.

Iovino F1, Molema G2, Bijlsma JJ1.

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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 co-localized with PECAM-1. Also in Human Brain Microvascular Endothelial Cells (HBMEC) incubated with S. pneumoniae we observed a clear co-localization 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 in vitro. Moreover, both in vitro and in vivo PECAM-1 co-localizes 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 co-localizes with PECAM-1 expressed by brain microvascular endothelium and that in addition they co-localize with pIgR. We hypothesize that this interaction may play a role in pneumococcal binding to the blood-brain barrier vasculature prior to invasion into the brain.

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PMID: 24914219 [PubMed - as supplied by publisher]