Trypanosoma brucei brucei: a model for cerebral trypanosomiasis in mice--an immunological, histological and electronmicroscopic study.
The successful induction of cerebral trypanosomiasis in ordinary laboratory mice using Trypanosoma brucei brucei is reported. Sequential studies demonstrated the presence of trypanosomes in the interstitium of the choroid plexus at the fourth week after infection which correlated with the appearance of anti-trypanosomal antibodies, a rise of IgM and IgG serum levels and a rise of Clq binding activity as well as a decrease of C3 levels. Electronmicroscopic studies showed that the parasites were flagellated and localized extracellularly mainly in the interstitium of the choroid plexus. Granular immunofluorescent deposits of Ig and C3 were most marked in the choroid plexus. Electron-dense deposits suggestive of immune complexes were seen in subendothelial, interstitial and subependymal areas of the choroid plexus. Since autoantibodies to the brain were found in the serum of some mice, the possible involvement of autoimmune manifestations in the pathogenesis of cerebral lesions has to be considered. The pattern of inflammatory foci at the eighth week after infection was very similar to that observed in cerebral African trypanosomiasis in man. After treatment with ethidium bromide, trypanosomes persisted in the tissues when circulating parasites could no longer be detected. These observations suggest a sequential involvement of brain structures during African trypanosomiasis. Trypanosomes may first migrate from the vascular compartment into the interstitium of the choroid plexus, possible favoured by increased vascular permeability. Circulating immune complexes and complement activation may be involved at this state. Trypanosomes localized in the choroid plexus may then trigger a local immunologically mediated inflammatory reaction favouring the migration of trypanosomes into the CSF and further invasion of other cerebral structures.
D000818:Animals; D001921:Brain / Q000276:immunology / Q000648:ultrastructure; D001927:Brain Diseases / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D004996:Ethidium / Q000627:therapeutic use; D005260:Female; D005455:Fluorescent Antibody Technique; D051379:Mice; D008854:Microscopy, Electron; D014346:Trypanosoma brucei brucei; D014353:Trypanosomiasis, African / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology
D004996:Ethidium