Back to Search
Start Over
Receptor Blockade: A Novel Approach to Protect the Brain From Pneumococcal Invasion
- Source :
- The Journal of infectious diseases. 218(3)
- Publication Year :
- 2017
-
Abstract
- Background Pneumococci are the major cause of bacterial meningitis globally. To cause meningitis pneumococci interact with the 2 endothelial receptors, polymeric immunoglobulin receptor (pIgR) and platelet endothelial cell adhesion molecule (PECAM-1), to penetrate the blood-brain barrier (BBB) and invade the brain. Methods C57BL/6 mice were infected intravenously with bioluminescent pneumococci, and treated with ceftriaxone (1 hour postinfection) and anti-pIgR and PECAM-1 antibodies (1 or 5 hours postinfection), then monitored for 5 and 10 days. Bacterial brain invasion was analyzed using IVIS imaging and bacterial counts. Results Ceftriaxone, given early after pneumococcal challenge, cleared pneumococci from the blood but not from the brain. After combining ceftriaxone with receptor blockade, using anti-pIgR and PECAM-1 antibodies, we found 100% survival after 5 and 10 days of infection, in contrast to 60% for ceftriaxone alone. Combined antibiotic and antibody treatment resulted in no or few viable bacteria in the brain and no microglia activation. Antibodies remained bound to the receptors during the study period. Receptor blockade did not interfere with antibiotic permeability through the BBB. Conclusions We suggest that adjunct treatment with pIgR and PECAM-1 antibodies to antibiotics may prevent pneumococcal meningitis development and associated brain damages. However, further evaluations are required.
- Subjects :
- 0301 basic medicine
Intravital Microscopy
medicine.drug_class
Antibiotics
Antibodies
Microbiology
03 medical and health sciences
0302 clinical medicine
Immunology and Allergy
Medicine
Animals
Receptor
biology
Microglia
business.industry
Meningitis, Pneumococcal
Ceftriaxone
Receptors, Polymeric Immunoglobulin
medicine.disease
Survival Analysis
Bacterial Load
Anti-Bacterial Agents
Mice, Inbred C57BL
Platelet Endothelial Cell Adhesion Molecule-1
Pneumococcal infections
Disease Models, Animal
030104 developmental biology
Infectious Diseases
medicine.anatomical_structure
Treatment Outcome
biology.protein
Drug Therapy, Combination
Antibody
business
Polymeric immunoglobulin receptor
Meningitis
030217 neurology & neurosurgery
medicine.drug
Subjects
Details
- ISSN :
- 15376613
- Volume :
- 218
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- The Journal of infectious diseases
- Accession number :
- edsair.doi.dedup.....9acc3fc3db02535b6ac9f5a62027d87c