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CC17 group B Streptococcus exploits integrins for neonatal meningitis development
- Source :
- The Journal of clinical investigation, The Journal of clinical investigation, 2021, 131 (5), pp.e136737. ⟨10.1172/JCI136737⟩, Journal of Clinical Investigation, Journal of Clinical Investigation, American Society for Clinical Investigation, 2021, 131 (5), ⟨10.1172/JCI136737⟩, J Clin Invest
- Publication Year :
- 2021
- Publisher :
- HAL CCSD, 2021.
-
Abstract
- We are grateful to Pierre-Olivier Couraud (INSERM, Paris, France) for the gift of hCMEC/D3 cells, Alain Duperray for the gift of CHO-ICAM1 cells, Yoshikazu Takada for the gift of CHO-αvβ3 cells, and Glen Ulett for the gift of the GFP plasmid. We are extremely grateful to Nathalie Strazielle and Jean-François Ghersi-Egea from BIP (CRNL, Lyon, France) for choroid plexus isolation and helpful comments. We thank Matthieu Benard from the animal facility of the Institut Cochin and Marine Gaillard for their help with animal experiments and Thomas Guilbert and Fabienne Regnier for their help with brain slice clarification. We also thank the Imag’IC and HistIM core facilities of the Cochin Institute and Shaynoor Dramsi for anti-Srr1 antibody and for critical reading of the manuscript.; International audience; Group B Streptococcus (GBS) is the major cause of human neonatal infections. A single clone, designated CC17-GBS, accounts for more than 80% of meningitis cases, the most severe form of the infection. However, the events allowing blood-borne GBS to penetrate the brain remain largely elusive. In this study, we identified the host transmembrane receptors α5β1 and αvβ3 integrins as the ligands of Srr2, a major CC17-GBS-specific adhesin. Two motifs located in the binding region of Srr2 were responsible for the interaction between CC17-GBS and these integrins. We demonstrated in a blood-brain-barrier cellular model that both integrins contributed to the adhesion and internalization of CC17-GBS. Strikingly, both integrins were overexpressed during the postnatal period in the brain vessels of the blood-brain barrier and blood-cerebrospinal fluid barrier and contributed to juvenile susceptibility to CC17 meningitis. Finally, blocking these integrins decreased the ability of CC17-GBS to cross into the CNS of juvenile mice in an in vivo model of meningitis. Our study demonstrated that CC17-GBS exploits integrins in order to cross the brain vessels, leading to meningitis. Importantly, it provides host molecular insights into neonate's susceptibility to CC17-GBS meningitis, thereby opening new perspectives for therapeutic and prevention strategies of GBS-elicited meningitis.
- Subjects :
- 0301 basic medicine
Group B Streptococcus
Integrins
[SDV]Life Sciences [q-bio]
[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology
Clone (cell biology)
medicine.disease_cause
Bacterial Adhesion
blood brain barrier (BBB)
0302 clinical medicine
Bacterial infections
[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases
Internalization
reproductive and urinary physiology
media_common
Infectious disease
Streptococcus
meningitis
General Medicine
3. Good health
Srr2
Blood-Brain Barrier
030220 oncology & carcinogenesis
[SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases
Meningitis
Research Article
integrin
media_common.quotation_subject
Integrin
Biology
Microbiology
Neonatal meningitis
Cell Line
Meningitis, Bacterial
Streptococcus agalactiae
03 medical and health sciences
[SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics
Streptococcal Infections
medicine
Animals
Humans
Receptors, Vitronectin
Adhesins, Bacterial
[SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics
[SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology
medicine.disease
Integrin alphaVbeta3
bacterial infections and mycoses
[SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology
Rats
Bacterial adhesin
030104 developmental biology
Animals, Newborn
biology.protein
neonatal susceptibility
bacteria
[SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology
CC17
Subjects
Details
- Language :
- English
- ISSN :
- 15588238 and 00219738
- Database :
- OpenAIRE
- Journal :
- The Journal of clinical investigation, The Journal of clinical investigation, 2021, 131 (5), pp.e136737. ⟨10.1172/JCI136737⟩, Journal of Clinical Investigation, Journal of Clinical Investigation, American Society for Clinical Investigation, 2021, 131 (5), ⟨10.1172/JCI136737⟩, J Clin Invest
- Accession number :
- edsair.doi.dedup.....9990e6b8af3856a03b1cd06d11fc1640