PUBLICATION

Targeting monocytic Occludin impairs transendothelial migration and HIV neuroinvasion

Authors
Brychka, D., Ayala-Nunez, N.V., Dupas, A., Bare, Y., Partiot, E., Mittelheisser, V., Lucansky, V., Goetz, J.G., Osmani, N., Gaudin, R.
ID
ZDB-PUB-240723-5
Date
2024
Source
EMBO reports   25(8): 3276-3299 (Journal)
Registered Authors
Keywords
AIDS, Central Nervous System, Endothelial Cells, Tight Junction, Zebrafish
MeSH Terms
  • HIV Infections/drug therapy
  • HIV Infections/virology
  • Transendothelial and Transepithelial Migration*/drug effects
  • Animals
  • Peptides/metabolism
  • Peptides/pharmacology
  • Occludin*/genetics
  • Occludin*/metabolism
  • Monocytes*/drug effects
  • Monocytes*/metabolism
  • Monocytes*/virology
  • Endothelial Cells*/drug effects
  • Endothelial Cells*/metabolism
  • Endothelial Cells*/virology
  • HIV-1/drug effects
  • HIV-1/physiology
  • Zebrafish*
  • Humans
  • Brain/metabolism
  • Brain/virology
(all 20)
PubMed
39039298 Full text @ EMBO Rep.
Abstract
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.
Genes / Markers
Figures
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Expression
Phenotype
No data available
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
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Citation
Brychka, D., Ayala-Nunez, N.V., Dupas, A., Bare, Y., Partiot, E., Mittelheisser, V., Lucansky, V., Goetz, J.G., Osmani, N., Gaudin, R. (2024) Targeting monocytic Occludin impairs transendothelial migration and HIV neuroinvasion. EMBO reports. 25(8):3276-3299.