Mode of Inoculation of the Lyme Disease Agent Borrelia burgdorferi Influences Infection and Immune Responses in Inbred Strains of Mice

Gern, Lise; Schaible, Ulrich E.; Simon, Markus M.

doi:10.1093/infdis/167.4.971

Cited by 100 publications

(81 citation statements)

References 15 publications

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“…The reason for this is the fact that the two routes of spirochete inoculation, i.e. tick versus needle infection, lead to greatly differing courses of infection, induction of immune responses and onset of disease manifestations [23,25,55]. However, it is clear that only the natural mode of infection will uncover strategies of either spirochetes or mammals which are of biological significance and thus of relevance for the appropriate treatment of Lyme disease.…”

Section: Discussionmentioning

confidence: 99%

“…In light of the notion that needle exposure by no means reflects the situation of tick infection [23,25,54] and the highly improved real-time PCR technique to quantify B. burgdorferi in situ [24,27,43,46,48,62,63,64], we have now performed a detailed quantitative analysis of the spirochete burden and population dynamics in different tissues of mice following natural (tick) infection by B. burgdorferi s.s. (ZS7) for a period of 4 months postinfection (p.i.). For this purpose we have selected one cp26-encoded gene, ospC [40], and four previously described lp54-encoded genes, i.e.…”

Section: Introductionmentioning

confidence: 99%

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Quantitative analysis of Borrelia burgdorferi gene expression in naturally (tick) infected mouse strains

Lederer

Brenner

Stehlé

et al. 2004

Med Microbiol Immunol

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Adaptation of Borrelia burgdorferi in the vector and vertebrate host is mediated by mechanisms that regulate differential expression of outer surface lipoproteins (Osps). In this study, real time PCR was applied to quantify tissue-specific expression of four linear plasmid (lp54)-encoded (ospA, zs7.a36, zs7.a66 zs7.a68) and one circular plasmid (cp26)-encoded (ospC) gene from B. burgdorferi sensu stricto, in a natural setting of tick-infected immunodeficient (C.B-17 SCID) and immunocompetent (BALB/c and AKR/OlaHsd) mice for up to 120 days post-infection (p.i.). Early during infection (day 30 p.i.) high numbers of spirochetes were found in the heart and joint, but not the ear and spleen tissues of disease-susceptible SCID mice. In diseasesusceptible AKR mice spirochetes colonized the ear and joint tissues, but were undetectable in tissues of diseaseresistant BALB/c mice. Later in infection (day 120 p.i.), spirochetes had expanded ($1,000-fold) in all SCID tissues tested but were undetectable in AKR and BALB/ c mice. Of the five genes analyzed, only zs7.a36 transcripts were detected in various tissues of all infected mouse strains, though at differing levels, whereas ospC transcripts were only found in tissue specimens of SCID mice. Furthermore, gene expression of ospC and zs7.a36 appears to be differentially regulated in distinct organs of individual mice. In contrast, transcripts for ospA, zs7.a66, and zs7.a68 were not detected in any of the mouse strains, independent of their immune status and/ or the severity of their infection/inflammatory responses. Late during infection (day 120 p.i.), transcription of zs7.a36 and ospC was down-regulated in the tissues of SCID mice despite expansion of spirochetes. This type of quantitative analysis may be helpful to further disclose principles of pathogenesis of Lyme borreliosis and to design strategies for its therapeutic treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Quantitative analysis of Borrelia burgdorferi gene expression in naturally (tick) infected mouse strains

Lederer

Brenner

Stehlé

et al. 2004

Med Microbiol Immunol

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“…Among isolates from the Aarberg area (site 3), 83% expressed the 21-23 kDa proteins and 76% reacted with PoAb anti-22 kDa/NE4 and this was significantly different from the isolates from site 1. Several studies showed that these proteins are important immunogens which elicit the antibody response early after the tick bite [5,[17][18][19]. It remains to be elucidated whether these proteins could be responsible for the presence of asymptomatic seropositive people in Aarberg by eliciting a protective antibody response.…”

Section: Discussionmentioning

confidence: 99%

Comparison in the immunological properties ofBorrelia burgdorferiisolates fromIxodes ricinusderived from three endemic areas in Switzerland

Leuba-Garcia

Kramer

et al. 1994

Epidemiol. Infect.

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SUMAIMARYBorrelia burgdorferi isolates were obtained from Ixodes ricinus from three sites in Switzerland. They were examined by SDS-PAGE and immunoblotting. The phenotypes, in respect of three outer surface proteins (Osp), differed between the sites of collection. In site 1, most isolates had an OspA of 31 kDa and an OspB of 34 kDa; in site 2, isolates presenting an OspA of 33 kDa dominated and in site 3, the isolates with an OspA of 32 kDa and an OspB of 35 kDa were most frequent. This distribution differed significantly. About half of the isolates from sites 1 and 3 reacted with anti-OspA monoclonal antibody H5332 compared to 29 % from site 2. Site 1 isolates reacted significantly more frequently (81 %) with another antiOspA monoclonal antibody LA-31 than isolates from site 3 (P < 0 0001). These findings have implications for the epidemiology of Lyme borreliosis, for the further development of serodiagnostic reagents and for the development of a vaccine.

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“…Based on their anatomic structure, the feeding apparatus of Ixodes ticks is adapted for imbibing accumulated tissue fluids from a cavity created in the skin of the host, 26,27 and dermal migration of spirochetes within hosts is suggested. 1,13,28 Our previous investigations also demonstrated that spirochetes can be acquired by the nymphal vector ticks as early as eight hours after tick attachment, and the efficiency of acquisition of spirochetes by feeding ticks was maximized (> 80%) at 48 hours after initial attachment of ticks. 14 Although differential acquisition of spirochetes by feeding ticks seems to be related to the span of time during which † Salivary gland extracts of unfed ticks (SGE0) or ticks that had fed on hosts for 2 days (SGE2), 4 days (SGE4), and 6 days (SGE6) were applied to the tops of the uninoculated sides and served as chemoattractant for inoculated spirochetes.…”

Section: Discussionmentioning

confidence: 84%

Chemotactic migration of the Lyme disease spirochete (Borrelia burgdorferi) to salivary gland extracts of vector ticks.

Shih¹,

Chao²,

Yu³

2002

The American Journal of Tropical Medicine and Hygiene

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Abstract. The migration of Lyme disease spirochetes (Borrelia burgdorferi) toward salivary gland extracts (SGEs) of vector ticks was determined by a modified U-tube chemotaxis assay. Responses of cultured spirochetes to the SGEs were measured by dark-field microscopy at intervals after the initial inoculation. The average numbers of spirochetes that migrated were compared between U-tubes containing either SGEs or phosphate-buffered saline (PBS). Spirochetes showed increased migration in tubes containing SGE, and migration was approximately 10-20-fold higher than that for spirochetes observed in tubes containing PBS. In addition, the span of migration showed no significant difference relative to the origin of spirochete isolation. These results demonstrate that spirochete migration can be enhanced by SGEs from fed vector ticks. This mechanism may contribute to the novel transmission of Lyme disease spirochetes between cofeeding infected and uninfected ticks in nature.

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Mode of Inoculation of the Lyme Disease Agent Borrelia burgdorferi Influences Infection and Immune Responses in Inbred Strains of Mice

Cited by 100 publications

References 15 publications

Quantitative analysis of Borrelia burgdorferi gene expression in naturally (tick) infected mouse strains

Quantitative analysis of Borrelia burgdorferi gene expression in naturally (tick) infected mouse strains

Comparison in the immunological properties ofBorrelia burgdorferiisolates fromIxodes ricinusderived from three endemic areas in Switzerland

Chemotactic migration of the Lyme disease spirochete (Borrelia burgdorferi) to salivary gland extracts of vector ticks.

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