Targeting monocytic Occludin impairs transendothelial migration and HIV neuroinvasion.
AIDS
Central Nervous System
Endothelial Cells
Tight Junction
Zebrafish
Journal
EMBO reports
ISSN: 1469-3178
Titre abrégé: EMBO Rep
Pays: England
ID NLM: 100963049
Informations de publication
Date de publication:
22 Jul 2024
22 Jul 2024
Historique:
received:
12
10
2023
accepted:
17
06
2024
revised:
11
06
2024
medline:
23
7
2024
pubmed:
23
7
2024
entrez:
22
7
2024
Statut:
aheadofprint
Résumé
Transmigration of circulating monocytes from the bloodstream to tissues represents an early hallmark of inflammation. This process plays a pivotal role during viral neuroinvasion, encephalitis, and HIV-associated neurocognitive disorders. How monocytes locally unzip endothelial tight junction-associated proteins (TJAPs), without perturbing impermeability, to reach the central nervous system remains poorly understood. Here, we show that human circulating monocytes express the TJAP Occludin (OCLN) to promote transmigration through endothelial cells. We found that human monocytic OCLN (hmOCLN) clusters at monocyte-endothelium interface, while modulation of hmOCLN expression significantly impacts monocyte transmigration. Furthermore, we designed OCLN-derived peptides targeting its extracellular loops (EL) and show that transmigration of treated monocytes is inhibited in vitro and in zebrafish embryos, while preserving vascular integrity. Monocyte transmigration toward the brain is an important process for HIV neuroinvasion and we found that the OCLN-derived peptides significantly inhibit HIV dissemination to cerebral organoids. In conclusion, our study identifies an important role for monocytic OCLN during transmigration and provides a proof-of-concept for the development of mitigation strategies to prevent monocyte infiltration and viral neuroinvasion.
Identifiants
pubmed: 39039298
doi: 10.1038/s44319-024-00190-x
pii: 10.1038/s44319-024-00190-x
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Agence Nationale de la Recherche (ANR)
ID : ANR-20-CE15-0019-01
Informations de copyright
© 2024. The Author(s).
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