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CD46 in meningococcal disease

Linda Johansson1, Anne Rytkonen, Peter Bergman

  • 1Microbiology and Tumor Biology Center, Nobels väg 16, Box 280, Karolinska Institutet, SE-171 77 Stockholm, Sweden.

Science (New York, N.Y.)
|July 19, 2003
PubMed

Insights

A new mouse model using human CD46 allows researchers to study how Neisseria meningitidis causes sepsis and meningitis. This model helps understand bacterial interactions with human cells for potential vaccine development.

Area of Science:

  • Microbiology
  • Immunology
  • Pathogenesis

Background:

  • Neisseria meningitidis is a human pathogen causing sepsis and meningitis.
  • Bacterial pili mediate interactions with host cell proteins like CD46.
  • CD46 regulates complement activation, a key immune response.

Purpose of the Study:

  • To investigate the role of human CD46 in Neisseria meningitidis pathogenesis.
  • To develop a relevant animal model for studying meningococcal disease.
  • To explore CD46-mediated bacterial entry into the central nervous system.

Main Methods:

  • Generation of transgenic mice expressing human CD46.
  • Intranasal and intraperitoneal challenge of mice with piliated and non-piliated N. meningitidis.
  • Assessment of bacterial translocation across the blood-brain barrier.

Main Results:

  • Transgenic mice expressing human CD46 were susceptible to meningococcal disease.
  • Piliated bacteria efficiently caused disease after intranasal challenge, indicating mucosal interaction.
  • Bacteria crossed the blood-brain barrier in CD46 transgenic mice.

Conclusions:

  • Human CD46 facilitates pilus-dependent interactions at the epithelial mucosa.
  • The human CD46 transgenic mouse model is valuable for studying N. meningitidis pathogenesis.
  • This model can aid in developing vaccines against meningococcal disease.

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