Skip to main content
PMC home page
Infection and Immunity logoLink to Infection and Immunity
. 1993 Jan;61(1):220–226. doi: 10.1128/iai.61.1.220-226.1993

Persistence of virulent Leishmania major in murine cutaneous leishmaniasis: a possible hazard for the host.

T Aebischer 1, S F Moody 1, E Handman 1
PMCID: PMC302708  PMID: 8093358

Abstract

The persistence of Leishmania major parasites in mice resistant to infection was investigated by the polymerase chain reaction and in vitro culture methods. Parasite-specific DNA was detected in the lymph nodes, spleens, bone marrow, and livers of C57BL/6 mice 1 year after their recovery from infection. Live parasites were also recovered from these tissues (except liver tissues) and were used to establish in vitro isolates. Pulsed-field gel electrophoresis, Southern blotting, and Western blot (immunoblot) analyses showed that these isolates retained the karyotype and the phenotype of the original inoculum, including the levels of expression of gp63 and lipophosphoglycan, the two major surface molecules of Leishmania species. More importantly, these isolates were virulent and induced fatal disease when injected into susceptible BALB/c mice. Persistence was shown to be a more general phenomenon, since several different strains of mice which were resistant to L. major infection also harbored persistent parasites. The implications for the etiology of human leishmaniasis in immunocompromised individuals such as AIDS patients are discussed.

Full text

PDF
220

Images in this article

222Image
on p.222
222Image
on p.222
223Image
on p.223
223Image
on p.223
224Image
on p.224

Selected References

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

  1. Bastien P., Blaineau C., Pages M. Leishmania: sex, lies and karyotype. Parasitol Today. 1992 May;8(5):174–177. doi: 10.1016/0169-4758(92)90016-u. [DOI] [PubMed] [Google Scholar]
  2. Bordier C. The promastigote surface protease of Leishmania. Parasitol Today. 1987 May;3(5):151–153. doi: 10.1016/0169-4758(87)90199-2. [DOI] [PubMed] [Google Scholar]
  3. Borst P. Discontinuous transcription and antigenic variation in trypanosomes. Annu Rev Biochem. 1986;55:701–732. doi: 10.1146/annurev.bi.55.070186.003413. [DOI] [PubMed] [Google Scholar]
  4. Button L. L., McMaster W. R. Molecular cloning of the major surface antigen of leishmania. J Exp Med. 1988 Feb 1;167(2):724–729. doi: 10.1084/jem.167.2.724. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Church G. M., Gilbert W. Genomic sequencing. Proc Natl Acad Sci U S A. 1984 Apr;81(7):1991–1995. doi: 10.1073/pnas.81.7.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Glaser T. A., Wells S. J., Spithill T. W., Pettitt J. M., Humphris D. C., Mukkada A. J. Leishmania major and L. donovani: a method for rapid purification of amastigotes. Exp Parasitol. 1990 Oct;71(3):343–345. doi: 10.1016/0014-4894(90)90039-f. [DOI] [PubMed] [Google Scholar]
  7. Gorczynski R. M. Altered virulence and vaccination properties of Leishmania parasites grown in infected vaccinated mice. Infect Immun. 1989 Aug;57(8):2430–2433. doi: 10.1128/iai.57.8.2430-2433.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Gorczynski R. M. Antigenic variation in Leishmania mexicana following infection of immunized mice leads to relative sparing of suppressor determinants. Immunol Lett. 1990 Jun;24(3):155–158. doi: 10.1016/0165-2478(90)90041-n. [DOI] [PubMed] [Google Scholar]
  9. Gray D., Matzinger P. T cell memory is short-lived in the absence of antigen. J Exp Med. 1991 Nov 1;174(5):969–974. doi: 10.1084/jem.174.5.969. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Greenblatt C. L., Slutzky G. M., de Ibarra A. A., Snary D. Monoclonal antibodies for serotyping Leishmania strains. J Clin Microbiol. 1983 Jul;18(1):191–193. doi: 10.1128/jcm.18.1.191-193.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Greenblatt C. L. The present and future of vaccination for cutaneous leishmaniasis. Prog Clin Biol Res. 1980;47:259–285. [PubMed] [Google Scholar]
  12. Handman E., Ceredig R., Mitchell G. F. Murine cutaneous leishmaniasis: disease patterns in intact and nude mice of various genotypes and examination of some differences between normal and infected macrophages. Aust J Exp Biol Med Sci. 1979 Feb;57(1):9–29. doi: 10.1038/icb.1979.2. [DOI] [PubMed] [Google Scholar]
  13. Handman E., Goding J. W. The Leishmania receptor for macrophages is a lipid-containing glycoconjugate. EMBO J. 1985 Feb;4(2):329–336. doi: 10.1002/j.1460-2075.1985.tb03633.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Handman E., Hocking R. E., Mitchell G. F., Spithill T. W. Isolation and characterization of infective and non-infective clones of Leishmania tropica. Mol Biochem Parasitol. 1983 Feb;7(2):111–126. doi: 10.1016/0166-6851(83)90039-7. [DOI] [PubMed] [Google Scholar]
  15. Handman E., Mitchell G. F., Goding J. W. Identification and characterization of protein antigens of Leishmania tropica isolates. J Immunol. 1981 Feb;126(2):508–512. [PubMed] [Google Scholar]
  16. Kelleher M., Bacic A., Handman E. Identification of a macrophage-binding determinant on lipophosphoglycan from Leishmania major promastigotes. Proc Natl Acad Sci U S A. 1992 Jan 1;89(1):6–10. doi: 10.1073/pnas.89.1.6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Leclerc C., Modabber F., Deriaud E., Cheddid L. Systemic infection of Leishmania tropica (major) in various strains of mice. Trans R Soc Trop Med Hyg. 1981;75(6):851–854. doi: 10.1016/0035-9203(81)90430-2. [DOI] [PubMed] [Google Scholar]
  18. Luft B. J., Castro K. G. An overview of the problem of toxoplasmosis and pneumocystosis in AIDS in the USA: implication for future therapeutic trials. Eur J Clin Microbiol Infect Dis. 1991 Mar;10(3):178–181. doi: 10.1007/BF01964455. [DOI] [PubMed] [Google Scholar]
  19. Meller-Melloul C., Farnarier C., Dunan S., Faugere B., Franck J., Mary C., Bongrand P., Quilici M., Kaplanski S. Evidence of subjects sensitized to Leishmania infantum on the French Mediterranean coast: differences in gamma interferon production between this population and visceral leishmaniasis patients. Parasite Immunol. 1991 Sep;13(5):531–536. doi: 10.1111/j.1365-3024.1991.tb00549.x. [DOI] [PubMed] [Google Scholar]
  20. Mitchell G. F. A note on concomitant immunity in host-parasite relationships: a successfully transplanted concept from tumor immunology. Adv Cancer Res. 1990;54:319–332. doi: 10.1016/s0065-230x(08)60816-7. [DOI] [PubMed] [Google Scholar]
  21. Modabber F. A model for the mechanism of sensitivity of BALB/c mice to L. major and premunition in leishmaniasis. Ann Inst Pasteur Immunol. 1987 Sep-Oct;138(5):781–786. doi: 10.1016/s0769-2625(87)80038-7. [DOI] [PubMed] [Google Scholar]
  22. Murray P. J., Handman E., Glaser T. A., Spithill T. W. Leishmania major: expression and gene structure of the glycoprotein 63 molecule in virulent and avirulent clones and strains. Exp Parasitol. 1990 Oct;71(3):294–304. doi: 10.1016/0014-4894(90)90034-a. [DOI] [PubMed] [Google Scholar]
  23. Murray P. J., Spithill T. W. Variants of a Leishmania surface antigen derived from a multigenic family. J Biol Chem. 1991 Dec 25;266(36):24477–24484. [PubMed] [Google Scholar]
  24. Oldstone M. B. Viral persistence. Cell. 1989 Feb 24;56(4):517–520. doi: 10.1016/0092-8674(89)90573-4. [DOI] [PubMed] [Google Scholar]
  25. Peters B. S., Fish D., Golden R., Evans D. A., Bryceson A. D., Pinching A. J. Visceral leishmaniasis in HIV infection and AIDS: clinical features and response to therapy. Q J Med. 1990 Nov;77(283):1101–1111. doi: 10.1093/qjmed/77.2.1101. [DOI] [PubMed] [Google Scholar]
  26. Pircher H., Moskophidis D., Rohrer U., Bürki K., Hengartner H., Zinkernagel R. M. Viral escape by selection of cytotoxic T cell-resistant virus variants in vivo. Nature. 1990 Aug 16;346(6285):629–633. doi: 10.1038/346629a0. [DOI] [PubMed] [Google Scholar]
  27. Preston P. M., Dumonde D. C. Experimental cutaneous leishmaniasis. V. Protective immunity in subclinical and self-healing infection in the mouse. Clin Exp Immunol. 1976 Jan;23(1):126–138. [PMC free article] [PubMed] [Google Scholar]
  28. Reiner N. E., Ng W., McMaster W. R. Parasite-accessory cell interactions in murine leishmaniasis. II. Leishmania donovani suppresses macrophage expression of class I and class II major histocompatibility complex gene products. J Immunol. 1987 Mar 15;138(6):1926–1932. [PubMed] [Google Scholar]
  29. Russell D. G., Wilhelm H. The involvement of the major surface glycoprotein (gp63) of Leishmania promastigotes in attachment to macrophages. J Immunol. 1986 Apr 1;136(7):2613–2620. [PubMed] [Google Scholar]
  30. Sacks D. L., Brodin T. N., Turco S. J. Developmental modification of the lipophosphoglycan from Leishmania major promastigotes during metacyclogenesis. Mol Biochem Parasitol. 1990 Sep-Oct;42(2):225–233. doi: 10.1016/0166-6851(90)90165-i. [DOI] [PubMed] [Google Scholar]
  31. Sacks D. L., da Silva R. P. The generation of infective stage Leishmania major promastigotes is associated with the cell-surface expression and release of a developmentally regulated glycolipid. J Immunol. 1987 Nov 1;139(9):3099–3106. [PubMed] [Google Scholar]
  32. Samaras N., Spithill T. W. The developmentally regulated P100/11E gene of Leishmania major shows homology to a superfamily of reductase genes. J Biol Chem. 1989 Mar 5;264(7):4251–4254. [PubMed] [Google Scholar]
  33. Schnur L., Zuckerman A., Montilio B. Dissemination of Leishmanias to the organs of Syrian hamsters following intrasplenic inoculation of promastigotes. Exp Parasitol. 1973 Dec;34(3):432–447. doi: 10.1016/0014-4894(73)90103-3. [DOI] [PubMed] [Google Scholar]
  34. Searle S., Campos A. J., Coulson R. M., Spithill T. W., Smith D. F. A family of heat shock protein 70-related genes are expressed in the promastigotes of Leishmania major. Nucleic Acids Res. 1989 Jul 11;17(13):5081–5095. doi: 10.1093/nar/17.13.5081. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. de Ibarra A. A., Howard J. G., Snary D. Monoclonal antibodies to Leishmania tropica major: specificities and antigen location. Parasitology. 1982 Dec;85(Pt 3):523–531. doi: 10.1017/s0031182000056304. [DOI] [PubMed] [Google Scholar]
  36. de Rossell R. A., de Duran R. J., Rossell O., Rodríguez A. M. Is leishmaniasis ever cured? Trans R Soc Trop Med Hyg. 1992 May-Jun;86(3):251–253. doi: 10.1016/0035-9203(92)90297-p. [DOI] [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES