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Humanized Mouse Model to Study Bacterial Infections Targeting the Microvasculature
11:40

Humanized Mouse Model to Study Bacterial Infections Targeting the Microvasculature

Published on: April 1, 2014

Meningococcus Hijacks a β2-adrenoceptor/β-Arrestin pathway to cross brain microvasculature endothelium

Mathieu Coureuil1, Hervé Lécuyer, Mark G H Scott

  • 1Université Paris Descartes, Faculté de Médecine, 75006 Paris, France.

Cell
|December 25, 2010
PubMed

Insights

Meningococcus hijacks brain endothelial cells via a specific beta-adrenoceptor pathway. This bacterial mechanism stabilizes adhesion and creates gaps for infection, offering new therapeutic targets.

Area of Science:

  • Microbiology
  • Cell Biology
  • Immunology

Background:

  • Neisseria meningitidis causes meningitis by colonizing human brain endothelial cells.
  • Meningococcal adhesion triggers host cell signaling, leading to junction opening and tissue invasion.
  • The specific host cell receptor mediating this process was previously unidentified.

Purpose of the Study:

  • To identify the host cell signaling receptor exploited by N. meningitidis during endothelial cell adhesion.
  • To elucidate the downstream signaling events and cellular mechanisms involved in meningococcal invasion.
  • To explore potential therapeutic strategies targeting this host-pathogen interaction.

Main Methods:

  • Investigated N. meningitidis interactions with human brain endothelial cells.
  • Utilized cell-based assays to identify the pathogen-activated signaling receptor.
  • Examined the roles of beta-arrestin, Src tyrosine kinase, and junctional proteins in bacterial adhesion and invasion.
  • Assessed the efficacy of beta-adrenoceptor agonists in blocking bacterial translocation.

Main Results:

  • N. meningitidis specifically activates a biased beta2-adrenoceptor/beta-arrestin signaling pathway in endothelial cells.
  • This pathway sequesters beta-arrestin interactors, including Src kinase and junctional proteins, beneath bacterial colonies.
  • Beta-arrestin-mediated Src activation stabilizes bacterial adhesion, while junctional protein delocalization creates invasion gaps.
  • Targeting beta-adrenoceptor endocytosis with agonists inhibited N. meningitidis translocation across the endothelial barrier.

Conclusions:

  • N. meningitidis hijacks the host beta2-adrenoceptor/beta-arrestin pathway for endothelial cell invasion.
  • The identified mechanism provides critical insights into meningococcal pathogenesis.
  • Targeting this specific host-pathogen interaction presents a promising avenue for developing novel anti-meningitis therapies.

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