title: Cyclical appearance of African trypanosomes in the cerebrospinal fluid: new insights in how trypanosomes enter the CNS.
abstract: It is textbook knowledge that human infective forms of Trypanosoma brucei, the causative agent of sleeping sickness, enter the brain across the blood-brain barrier after an initial phase of weeks (rhodesiense) or months (gambiense) in blood. Based on our results using an animal model, both statements seem questionable. As we and others have shown, the first infection relevant crossing of the blood brain border occurs via the choroid plexus, i.e. via the blood-CSF barrier. In addition, counting trypanosomes in blood-free CSF obtained by an atlanto-occipital access revealed a cyclical infection in CSF that was directly correlated to the trypanosome density in blood infection. We also obtained conclusive evidence of organ infiltration, since parasites were detected in tissues outside the blood vessels in heart, spleen, liver, eye, testis, epididymis, and especially between the cell layers of the pia mater including the Virchow-Robin space. Interestingly, in all organs except pia mater, heart and testis, trypanosomes showed either a more or less degraded appearance of cell integrity by loss of the surface coat (VSG), loss of the microtubular cytoskeleton and loss of the intracellular content, or where taken up by phagocytes and degraded intracellularly within lysosomes. This is also true for trypanosomes placed intrathecally into the brain parenchyma using a stereotactic device. We propose a different model of brain infection that is in accordance with our observations and with well-established facts about the development of sleeping sickness.
authors.affiliation: Interfaculty Institute of Biochemistry, University of Tübingen, Tübingen, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Mogk
authors.affiliation: Interfaculty Institute of Biochemistry, University of Tübingen, Tübingen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Meiwes
authors.affiliation: Interfaculty Institute of Biochemistry, University of Tübingen, Tübingen, Germany.
authors.forename: Swetlana
authors.initials: S
authors.lastname: Shtopel
authors.affiliation: Institute of Ophthalmology, University of Tübingen, Tübingen, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Schraermeyer
authors.affiliation: International Institute for Integrative Sleep Medicine, University of Tsukuba, Tsukuba, Japan.
authors.forename: Michael
authors.initials: M
authors.lastname: Lazarus
authors.affiliation: AU/NEPAD Agency Regional Office, Nairobi, Kenya.
authors.forename: Bruno
authors.initials: B
authors.lastname: Kubata
authors.affiliation: Institute of Pathology and Neuropathology, University of Tübingen, Tübingen, Germany.
authors.forename: Hartwig
authors.initials: H
authors.lastname: Wolburg
authors.affiliation: Interfaculty Institute of Biochemistry, University of Tübingen, Tübingen, Germany; Faculty of Medicine and Life Sciences, Tongji University, Shanghai, P. R. China.
authors.forename: Michael
authors.initials: M
authors.lastname: Duszenko
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000134:cerebrospinal fluid / Q000276:immunology; D001812:Blood-Brain Barrier / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D001921:Brain / Q000469:parasitology / Q000473:pathology / Q000648:ultrastructure; D002490:Central Nervous System / Q000469:parasitology / Q000473:pathology; D002555:Cerebrospinal Fluid / Q000276:immunology / Q000469:parasitology*; D062445:Claudin-1 / Q000378:metabolism; D006801:Humans; D010841:Pia Mater / Q000469:parasitology / Q000648:ultrastructure; D051381:Rats; D014347:Trypanosoma brucei gambiense / Q000276:immunology; D014353:Trypanosomiasis, African / Q000276:immunology / Q000378:metabolism / Q000469:parasitology* / Q000473:pathology
chemical_list: D000913:Antibodies, Protozoan; D062445:Claudin-1