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Streptococcus pneumoniae Interacts with pIgR expressed by the brain microvascular endothelium but does not
Federico Iovino1, Grietje Molema2, Jetta J E Bijlsma1
1Department of Medical Microbiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Abstract:
Streptococcus pneumoniae is thought to adhere to the blood-brain barrier (BBB) endothelium prior to causing meningitis. The platelet activating factor receptor (PAFR) has been implicated in this adhesion but there is a paucity of data demonstrating direct binding of the bacteria to PAFR. Additionally, studies that inhibit PAFR strongly suggest that alternative receptors for pneumococci are present on the endothelium. Therefore, we studied the roles of PAFR and pIgR, an established epithelial pneumococcal receptor, in pneumococcal adhesion to brain endothelial cells in vivo. Mice were intravenously infected with pneumococci and sacrificed at various time points before meningitis onset. Co-localization of bacteria with PAFR and pIgR was investigated using immunofluorescent analysis of the brain tissue. In vitro blocking with antibodies and incubation of pneumococci with endothelial cell lysates were used to further probe bacteria-receptor interaction. In vivo as well as in vitro pneumococci did not co-localize with PAFR. On the other hand the majority of S. pneumoniae co-localized with endothelial pIgR and pIgR blocking reduced pneumococcal adhesion to endothelial cells. Pneumococci physically interacted with pIgR in endothelial cell lysates. In conclusion, bacteria did not associate with PAFR, indicating an indirect role of PAFR in pneumococcal adhesion to endothelial cells. In contrast, pIgR on the BBB endothelium may represent a novel pneumococcal adhesion receptor.
Insights
Streptococcus pneumoniae does not directly bind to platelet activating factor receptor (PAFR) on brain endothelial cells. Instead, the study reveals Polymeric immunoglobulin receptor (pIgR) as a potential novel adhesion receptor for pneumococci on the blood-brain barrier.
Area of Science:
- Neuroscience
- Microbiology
- Immunology
Background:
- Streptococcus pneumoniae adhesion to the blood-brain barrier (BBB) endothelium is a critical step in meningitis development.
- Platelet activating factor receptor (PAFR) has been suggested to mediate this adhesion, but direct evidence is lacking, and alternative receptors are suspected.
Purpose of the Study:
- To investigate the roles of PAFR and Polymeric immunoglobulin receptor (pIgR) in pneumococcal adhesion to brain endothelial cells in vivo.
- To determine if PAFR or pIgR serve as direct binding sites for Streptococcus pneumoniae on the BBB endothelium.
Main Methods:
- In vivo studies using a mouse model infected with Streptococcus pneumoniae, followed by immunofluorescent analysis of brain tissue.
- In vitro experiments involving antibody blocking and incubation of bacteria with endothelial cell lysates to assess receptor interactions.
Main Results:
- Streptococcus pneumoniae did not co-localize with PAFR in vivo or in vitro.
- A majority of S. pneumoniae co-localized with endothelial pIgR.
- Blocking pIgR significantly reduced pneumococcal adhesion to endothelial cells.
- Physical interaction between pneumococci and pIgR was observed in endothelial cell lysates.
Conclusions:
- PAFR plays an indirect role in pneumococcal adhesion to endothelial cells.
- Endothelial pIgR represents a potential novel receptor for Streptococcus pneumoniae adhesion at the BBB.
- These findings challenge the established role of PAFR and highlight pIgR as a new target for therapeutic intervention.