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Meningococcal outer membrane protein NhhA triggers apoptosis in macrophages

Mikael Sjölinder1, Georg Altenbacher, Matthias Hagner

  • 1Department of Genetics, Microbiology and Toxicology, Stockholm University, Stockholm, Sweden.

Plos One
|January 13, 2012
PubMed

Insights

The meningococcal protein NhhA induces macrophage apoptosis, a process crucial for bacterial evasion of immune defenses. This discovery sheds light on how Neisseria meningitidis evades phagocytosis and causes disease.

Area of Science:

  • Immunology
  • Microbiology
  • Cell Biology

Background:

  • Phagocytotic cells are vital for combating bacterial pathogens.
  • Bacteria can evade phagocytosis by inducing apoptosis in immune cells.
  • The role of specific bacterial proteins in this evasion is not fully understood.

Purpose of the Study:

  • To identify and characterize meningococcal proteins that induce macrophage apoptosis.
  • To elucidate the mechanism by which Neisseria meningitidis evades phagocytosis.
  • To investigate the role of the NhhA protein in meningococcal pathogenesis.

Main Methods:

  • Macrophage apoptosis assays upon exposure to purified NhhA protein.
  • Analysis of caspase activation and nitric oxide production.
  • Comparison of apoptosis induction by wildtype and NhhA-deficient Neisseria meningitidis strains in macrophages.
  • Assessment of nasal colonization in a mouse model.

Main Results:

  • The meningococcal outer membrane protein NhhA was identified as a potent inducer of macrophage apoptosis via caspase activation.
  • NhhA mediates bacterial adhesion and interaction with heparan sulfate and laminin.
  • Mice infected with NhhA-deficient meningococci showed reduced nasal colonization.
  • NhhA-expressing meningococci induced significantly more macrophage apoptosis than NhhA-deficient strains.

Conclusions:

  • NhhA is a key factor in Neisseria meningitidis pathogenesis, contributing to immune evasion.
  • NhhA-induced macrophage apoptosis is a mechanism by which meningococci avoid phagocytosis and immune surveillance.
  • Targeting NhhA may represent a novel therapeutic strategy against meningococcal infections.

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