Skip to main content
PMC home page
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1993 Sep;143(3):959–971.

Chronic Lyme borreliosis in the laboratory mouse.

S W Barthold 1, M S de Souza 1, J L Janotka 1, A L Smith 1, D H Persing 1
PMCID: PMC1887206  PMID: 8362988

Abstract

C3H/HeJ mice were inoculated intraperitoneally with 10(7) uncloned Borrelia burgdorferi at 4 weeks of age and examined on days 30, 90, 180, and 360. Spirochetes were isolated from multiple tissues at all intervals. Joint and heart disease were present in all mice at 30 days and resolved after 90 days. At 180 and 360 days, some mice had mild recurrent joint and heart disease, and most had peripheral segmental periarteritis. The protein electrophoretic migration of 360-day isolates differed from the original inoculum. The experiment was repeated with C3H/HeN and BALB/cByJ mice inoculated intradermally with 10(4) cloned B. burgdorferi. Characterization of infection and disease at 180 and 360 days were similar to those of the first experiment, but spirochetal proteins of isolates from both intervals displayed no protein variation in electrophoretic mobilities. Spirochetes isolated at 360 days were fully pathogenic in naive mice. Sera from infected mice showed an initial immunoglobulin M response, followed by a sustained immunoglobulin G response, involving IgG1, IgG2a, IgG2b and IgG3, with expanding reactivity against multiple antigens over time. These results indicate that immunocompetent mice sustain persistent infections and develop early acute joint and heart lesions that resolve and then recur intermittently.

Full text

PDF
959

Images in this article

963Figure 1
on p.963
964Figure 2
on p.964
965Figure 3
on p.965
966Figure 4
on p.966
968Figure 5
on p.968

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Armstrong A. L., Barthold S. W., Persing D. H., Beck D. S. Carditis in Lyme disease susceptible and resistant strains of laboratory mice infected with Borrelia burgdorferi. Am J Trop Med Hyg. 1992 Aug;47(2):249–258. doi: 10.4269/ajtmh.1992.47.249. [DOI] [PubMed] [Google Scholar]
  2. Asbrink E., Hovmark A. Successful cultivation of spirochetes from skin lesions of patients with erythema chronicum migrans Afzelius and acrodermatitis chronica atrophicans. Acta Pathol Microbiol Immunol Scand B. 1985 Apr;93(2):161–163. doi: 10.1111/j.1699-0463.1985.tb02870.x. [DOI] [PubMed] [Google Scholar]
  3. Barbour A. G. Isolation and cultivation of Lyme disease spirochetes. Yale J Biol Med. 1984 Jul-Aug;57(4):521–525. [PMC free article] [PubMed] [Google Scholar]
  4. Barthold S. W., Beck D. S., Hansen G. M., Terwilliger G. A., Moody K. D. Lyme borreliosis in selected strains and ages of laboratory mice. J Infect Dis. 1990 Jul;162(1):133–138. doi: 10.1093/infdis/162.1.133. [DOI] [PubMed] [Google Scholar]
  5. Barthold S. W. Infectivity of Borrelia burgdorferi relative to route of inoculation and genotype in laboratory mice. J Infect Dis. 1991 Feb;163(2):419–420. doi: 10.1093/infdis/163.2.419. [DOI] [PubMed] [Google Scholar]
  6. Barthold S. W., Persing D. H., Armstrong A. L., Peeples R. A. Kinetics of Borrelia burgdorferi dissemination and evolution of disease after intradermal inoculation of mice. Am J Pathol. 1991 Aug;139(2):263–273. [PMC free article] [PubMed] [Google Scholar]
  7. Barthold S. W., Sidman C. L., Smith A. L. Lyme borreliosis in genetically resistant and susceptible mice with severe combined immunodeficiency. Am J Trop Med Hyg. 1992 Nov;47(5):605–613. doi: 10.4269/ajtmh.1992.47.605. [DOI] [PubMed] [Google Scholar]
  8. Craft J. E., Fischer D. K., Shimamoto G. T., Steere A. C. Antigens of Borrelia burgdorferi recognized during Lyme disease. Appearance of a new immunoglobulin M response and expansion of the immunoglobulin G response late in the illness. J Clin Invest. 1986 Oct;78(4):934–939. doi: 10.1172/JCI112683. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Duray P. H., Johnson R. C. The histopathology of experimentally infected hamsters with the Lyme disease spirochete, Borrelia burgdorferi. Proc Soc Exp Biol Med. 1986 Feb;181(2):263–269. doi: 10.3181/00379727-181-42251. [DOI] [PubMed] [Google Scholar]
  10. Fikrig E., Tao H., Kantor F. S., Barthold S. W., Flavell R. A. Evasion of protective immunity by Borrelia burgdorferi by truncation of outer surface protein B. Proc Natl Acad Sci U S A. 1993 May 1;90(9):4092–4096. doi: 10.1073/pnas.90.9.4092. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Johnson R. C., Marek N., Kodner C. Infection of Syrian hamsters with Lyme disease spirochetes. J Clin Microbiol. 1984 Dec;20(6):1099–1101. doi: 10.1128/jcm.20.6.1099-1101.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Luft B. J., Jiang W., Munoz P., Dattwyler R. J., Gorevic P. D. Biochemical and immunological characterization of the surface proteins of Borrelia burgdorferi. Infect Immun. 1989 Nov;57(11):3637–3645. doi: 10.1128/iai.57.11.3637-3645.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Moody K. D., Barthold S. W., Terwilliger G. A., Beck D. S., Hansen G. M., Jacoby R. O. Experimental chronic Lyme borreliosis in Lewis rats. Am J Trop Med Hyg. 1990 Feb;42(2):165–174. doi: 10.4269/ajtmh.1990.42.165. [DOI] [PubMed] [Google Scholar]
  14. Rosa P. A., Schwan T., Hogan D. Recombination between genes encoding major outer surface proteins A and B of Borrelia burgdorferi. Mol Microbiol. 1992 Oct;6(20):3031–3040. doi: 10.1111/j.1365-2958.1992.tb01761.x. [DOI] [PubMed] [Google Scholar]
  15. Schaible U. E., Kramer M. D., Wallich R., Tran T., Simon M. M. Experimental Borrelia burgdorferi infection in inbred mouse strains: antibody response and association of H-2 genes with resistance and susceptibility to development of arthritis. Eur J Immunol. 1991 Oct;21(10):2397–2405. doi: 10.1002/eji.1830211016. [DOI] [PubMed] [Google Scholar]
  16. Schmitz J. L., Schell R. F., Hejka A., England D. M., Konick L. Induction of lyme arthritis in LSH hamsters. Infect Immun. 1988 Sep;56(9):2336–2342. doi: 10.1128/iai.56.9.2336-2342.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Schwan T. G., Kime K. K., Schrumpf M. E., Coe J. E., Simpson W. J. Antibody response in white-footed mice (Peromyscus leucopus) experimentally infected with the Lyme disease spirochete (Borrelia burgdorferi). Infect Immun. 1989 Nov;57(11):3445–3451. doi: 10.1128/iai.57.11.3445-3451.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Sears J. E., Fikrig E., Nakagawa T. Y., Deponte K., Marcantonio N., Kantor F. S., Flavell R. A. Molecular mapping of Osp-A mediated immunity against Borrelia burgdorferi, the agent of Lyme disease. J Immunol. 1991 Sep 15;147(6):1995–2000. [PubMed] [Google Scholar]
  19. Simpson W. J., Burgdorfer W., Schrumpf M. E., Karstens R. H., Schwan T. G. Antibody to a 39-kilodalton Borrelia burgdorferi antigen (P39) as a marker for infection in experimentally and naturally inoculated animals. J Clin Microbiol. 1991 Feb;29(2):236–243. doi: 10.1128/jcm.29.2.236-243.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Simpson W. J., Schrumpf M. E., Schwan T. G. Reactivity of human Lyme borreliosis sera with a 39-kilodalton antigen specific to Borrelia burgdorferi. J Clin Microbiol. 1990 Jun;28(6):1329–1337. doi: 10.1128/jcm.28.6.1329-1337.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Snydman D. R., Schenkein D. P., Berardi V. P., Lastavica C. C., Pariser K. M. Borrelia burgdorferi in joint fluid in chronic Lyme arthritis. Ann Intern Med. 1986 Jun;104(6):798–800. doi: 10.7326/0003-4819-104-6-798. [DOI] [PubMed] [Google Scholar]
  22. Stanek G., Klein J., Bittner R., Glogar D. Isolation of Borrelia burgdorferi from the myocardium of a patient with longstanding cardiomyopathy. N Engl J Med. 1990 Jan 25;322(4):249–252. doi: 10.1056/NEJM199001253220407. [DOI] [PubMed] [Google Scholar]
  23. Steere A. C., Dwyer E., Winchester R. Association of chronic Lyme arthritis with HLA-DR4 and HLA-DR2 alleles. N Engl J Med. 1990 Jul 26;323(4):219–223. doi: 10.1056/NEJM199007263230402. [DOI] [PubMed] [Google Scholar]
  24. Steere A. C. Lyme disease. N Engl J Med. 1989 Aug 31;321(9):586–596. doi: 10.1056/NEJM198908313210906. [DOI] [PubMed] [Google Scholar]
  25. Steere A. C., Schoen R. T., Taylor E. The clinical evolution of Lyme arthritis. Ann Intern Med. 1987 Nov;107(5):725–731. doi: 10.7326/0003-4819-107-5-725. [DOI] [PubMed] [Google Scholar]
  26. Sădziene A., Rosa P. A., Thompson P. A., Hogan D. M., Barbour A. G. Antibody-resistant mutants of Borrelia burgdorferi: in vitro selection and characterization. J Exp Med. 1992 Sep 1;176(3):799–809. doi: 10.1084/jem.176.3.799. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. de Souza M. S., Fikrig E., Smith A. L., Flavell R. A., Barthold S. W. Nonspecific proliferative responses of murine lymphocytes to Borrelia burgdorferi antigens. J Infect Dis. 1992 Mar;165(3):471–478. doi: 10.1093/infdis/165.3.471. [DOI] [PubMed] [Google Scholar]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES