Antibodies directed to the gram-negative bacterium Neisseria gonorrhoeae cross-react with the 60 kDa heat shock protein and lead to impaired neurite outgrowth in NTera2/D1 cells

J Mol Neurosci. 2014 Sep;54(1):125-36. doi: 10.1007/s12031-014-0258-y. Epub 2014 Feb 28.

Abstract

Children of mothers with prenatal gonococcal infections are of increased risk to develop schizophrenic psychosis in later life. The present study hypothesizes an autoimmune mechanism for this, investigating interactions of a commercial rabbit antiserum directed to Neisseria gonorrhoeae (α-NG) with human NTera2/D1 cells, an established in vitro model for human neuronal differentiation. Immunocytochemistry demonstrated α-NG to label antigens on an intracellular organelle, which by Western blot analysis showed a molecular weight shortly below 72 kDa. An antiserum directed to Neisseria meningitidis (α-NM) reacts with an antigen shortly below 95 kDa, confirming antibody specificity of these interactions. Two-dimensional gel electrophoresis and partial Western transfer, allowed to localize an α-NG reactive protein spot which was identified by LC-Q-TOF MS/MS analysis as mitochondrial heat shock protein Hsp60. This was confirmed by Western blot analysis of α-NG immunoreactivity with a commercial Hsp60 protein sample, with which α-NM failed to interact. Finally, analysis of neurite outgrowth in retinoic acid-stimulated differentiating NTera2-D1 cells, demonstrates that α-NG but not α-NM treatment reduces neurite length. These results demonstrate that α-NG can interact with Hsp60 in vitro, whereas pathogenetic relevance of this interaction for psychotic symptomatology remains to be clarified.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Bacterial / immunology
  • Antibodies, Bacterial / toxicity*
  • Cell Line, Tumor
  • Chaperonin 60 / immunology*
  • Cross Reactions*
  • Humans
  • Mitochondrial Proteins / immunology*
  • Neisseria gonorrhoeae / immunology*
  • Neisseria meningitidis / immunology
  • Neurites / drug effects*
  • Neurites / physiology
  • Neurogenesis / drug effects
  • Schizophrenia / etiology

Substances

  • Antibodies, Bacterial
  • Chaperonin 60
  • HSPD1 protein, human
  • Mitochondrial Proteins