title: 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.
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.
authors.affiliation: Institute for Neuroanatomy, Universitary Medicine Göttingen (UMG), Kreuzbergring 36, 37075, Göttingen, Germany, breuss@gwdg.de.
authors.forename: B
authors.initials: B
authors.lastname: Reuss
authors.forename: A R
authors.initials: AR
authors.lastname: Asif
mesh_terms: D000907:Antibodies, Bacterial / Q000276:immunology / Q000633:toxicity*; D045744:Cell Line, Tumor; D018834:Chaperonin 60 / Q000276:immunology*; D003429:Cross Reactions; D006801:Humans; D024101:Mitochondrial Proteins / Q000276:immunology*; D009344:Neisseria gonorrhoeae / Q000276:immunology*; D009345:Neisseria meningitidis / Q000276:immunology; D016501:Neurites / Q000187:drug effects* / Q000502:physiology; D055495:Neurogenesis / Q000187:drug effects; D012559:Schizophrenia / Q000209:etiology
chemical_list: D000907:Antibodies, Bacterial; D018834:Chaperonin 60; C060293:HSPD1 protein, human; D024101:Mitochondrial Proteins