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Gern, Lise

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Gern, Lise
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Ancien.ne collaborateur.trice
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https://libra.unine.ch/handle/123456789/303

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  • Publication
    Métadonnées seulement
    Borrelia burgdorferi persists in the brain in chronic lyme neuroborreliosis and may be associated with Alzheimer disease
    (2004)
    Miklossy, Judith
    ;
    Khalili, Kamel
    ;
    Gern, Lise 
    ;
    Ericson, Rebecca L
    ;
    Darekar, Pushpa
    ;
    Bolle, Lorie
    ;
    Hurlimann, Jean
    ;
    Paster, Bruce J
    The cause, or causes, of the vast majority of Alzheimer's disease cases are unknown. A number of contributing factors have been postulated, including infection. It has long been known that the spirochete Teponema pallidum, which is the infective agent for syphilis, can in its late stages cause dementia, chronic inflammation, cortical atrophy and amyloid deposition. Spirochetes of unidentified types and strains have previously been observed in the blood, CSF and brain of 14 AD patients tested and absent in 13 controls. In three of these AD cases spirochetes were grown in a medium selective for Borrelia burgdorferi. In the present study, the phylogenetic analysis of these spirochetes was made. Positive identification of the agent as Borrelia burgdorferi sensu stricto was based on genetic and molecular analyses. Borrelia antigens and genes were co-localized with beta-amyloid deposits in these AD cases. The data indicate that Borrelia burgdorferi may persist in the brain and be associated with amyloid plaques in AD. They suggest that these spirochetes, perhaps in an analogous fashion to Treponema pallidum, may contribute to dementia, cortical atrophy and amyloid deposition. Further in vitro and in vivo studies may bring more insight into the potential role of spirochetes in AD.
  • Publication
    Métadonnées seulement
    Artificial-infection protocols allow immunodetection of novel Borrelia burgdorferi antigens suitable as vaccine candidates against Lyme disease
    (2003)
    Wallich, Reinhard
    ;
    Jahraus, Oliver
    ;
    Stehle, Thomas
    ;
    Tran, Thi Thanh Thao
    ;
    Brenner, Christiane
    ;
    Hofmann, Heidelore
    ;
    Gern, Lise 
    ;
    Simon, Markus M
    Vaccination with recombinant outer surface protein A (OspA) from Borrelia burgdorferi provides excellent antibody-mediated protection against challenge with the pathogen in animal models and in humans. However, the bactericidal antibodies are ineffective in the reservoir host, since OspA is expressed by spirochetes only in the vector, but rarely, if at all, in mammals. Using an artificially generated immune serum (anti-10(8) spirochetes) with high protective potential for prophylactic and therapeutic treatment, we have now isolated from an expression library of B. burgdorferi (strain ZS7) three novel genes, zs7.a36, zs7.a66 and zs7.a68. All three genes are located, together with ospA/B, on the linear plasmid lp54, and are expressed in vitro and in ticks. At least temporarily two of them, ZS7.A36 and ZS7.A66, are also expressed during infection. The respective natural antigens are poorly immunogenic in infected normal mice but elicited antibodies in Lyme disease patients. We show that recombinant preparations of ZS7.A36, ZS7.A66 and ZS7.A68 induce functional antibodies in rabbits capable of protecting immunodeficient mice against subsequent experimental infection. These findings suggest that all three recombinant antigens represent potential candidates for a 'second generation' vaccine to prevent and/or cure Lyme disease.
  • Publication
    Métadonnées seulement
    Dynamics of dissemination and outer surface protein expression of different European Borrelia burgdorferi sensu lato strains in artificially infected Ixodes ricinus nymphs
    (2002)
    Fingerle, Volker
    ;
    Rauser, Sandra
    ;
    Hammer, Bettina
    ;
    Kahl, Olaf
    ;
    Heimerl, Christiane
    ;
    Schulte-Spechtel, Ulrike
    ;
    Gern, Lise 
    ;
    Wilske, Bettina
    Unfed Ixodes ricinus nymphs were infected with eight different strains and clones of Borrelia afzelii and B. garinii by capillary feeding. Except one B. afzelii clone, all expressed OspC in culture. Tick midguts and salivary glands were investigated at different time intervals for the presence of borreliae and for OspA and OspC phenotypes by immunofluorescence with simultaneous staining of OspA and OspC with monoclonal antibodies. Both species were transmittable to L ricinus. All OspC-expressing strains and clones were able to disseminate into the salivary glands. In contrast, the OspC-negative B. afzelii clone was not detectable in the salivary glands, an indication that OspC plays an important role in dissemination. OspA-positive borreliae prevailed in the midgut. OspC positives were more frequent in the salivary glands than in the midgut. Notably, simultaneously OspA- and OspC-negative borreliae were detected in both organs. Kinetics of dissemination varied with the strains. The OspC-positive B. afzelii clone and all B. garinii OspA type 4 strains were detectable in the salivary glands right after feeding, while one B. garinii OspA type 6 strain invaded the salivary glands with a delay of 24 h. These findings support the hypothesis that OspA is abundantly expressed in unfed ticks while upregulation of OspC is also a prerequisite for dissemination in the vector for the Eurasian species B. afzelii and B. garinii. However, we found strain-specific dynamics of Osp expression and strain-specific kinetics of systemic infection in the vector tick and it appears that additional factors are involved in the initiation and regulation of the dissemination process.