Skip to main content
PMC home page
Immunology logoLink to Immunology
. 1995 Jan;84(1):1–4.

Sex-determined susceptibility and differential IFN-gamma and TNF-alpha mRNA expression in DBA/2 mice infected with Leishmania mexicana.

A Satoskar 1, J Alexander 1
PMCID: PMC1415181  PMID: 7890293

Abstract

Female DBA/2 mice have been shown to be relatively resistant to infection with Leishmania mexicana when compared with male mice. In order to determine the immunological basis behind this difference the draining lymph nodes from male and female DBA/2 mice were excised and the RNA extracted at different time-points following infection. Following reverse transcription, the polymerase chain reaction (PCR) was used to identify mRNA transcripts for interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha), interleukin-4 (IL-4), IL-10 and IL-12. The evolution of cytokine mRNA production was slow in both male and female mice as no newly synthesized transcripts were identified 5 weeks after infection. IL-10 was expressed constitutively in non-infected mice and was present throughout the experiment in all animals. By week 8, a clear dichotomy in cytokine mRNA expression was emerging between the resistant female and susceptible male mice. Whereas all females expressed IFN-gamma and one also expressed TNF-alpha only two out of five males expressed IFN-gamma and four out of five expressed TNF-alpha. The greatest lesion sizes at this time were recorded from those mice expressing TNF-alpha but not IFN-gamma. No differences in IL-4 or IL-12 were noted with transcripts for both cytokines present in both sexes at week 8. By week 12 males had developed large non-healing nodules and in females lesions had either disappeared or were slow growing. At this time only transcripts for TNF-alpha were present in males and only those for IFN-gamma were detected in females. Treatment of female mice following infection with IFN-gamma neutralizing antibody resulted in lesion growth equivalent to male mice. IFN-gamma production would, therefore, appear sufficient to limit the growth of L. mexicana in female DBA/2 mice while TNF-alpha production in the absence of IFN-gamma confers no protection to DBA/2 male mice.

Full text

PDF
3

Images in this article

2Figure 2
on p.2
3Figure 3
on p.3

Selected References

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

  1. Alexander J., Kaye P. M. Immunoregulatory pathways in murine leishmaniasis: different regulatory control during Leishmania mexicana mexicana and Leishmania major infections. Clin Exp Immunol. 1985 Sep;61(3):674–682. [PMC free article] [PubMed] [Google Scholar]
  2. Alexander J., Phillips R. S. Leishmania tropica and Leishmania mexicana: cross-immunity in mice. Exp Parasitol. 1978 Jun;45(1):93–100. doi: 10.1016/0014-4894(78)90049-8. [DOI] [PubMed] [Google Scholar]
  3. Alexander J. Sex differences and cross-immunity in DBA/2 mice infected with L. mexicana and L. major. Parasitology. 1988 Apr;96(Pt 2):297–302. doi: 10.1017/s0031182000058303. [DOI] [PubMed] [Google Scholar]
  4. Alexander J., Vickerman K. Fusion of host cell secondary lysosomes with the parasitophorous vacuoles of Leishmania mexicana-infected macrophages. J Protozool. 1975 Nov;22(4):502–508. doi: 10.1111/j.1550-7408.1975.tb05219.x. [DOI] [PubMed] [Google Scholar]
  5. Bogdan C., Moll H., Solbach W., Röllinghoff M. Tumor necrosis factor-alpha in combination with interferon-gamma, but not with interleukin 4 activates murine macrophages for elimination of Leishmania major amastigotes. Eur J Immunol. 1990 May;20(5):1131–1135. doi: 10.1002/eji.1830200528. [DOI] [PubMed] [Google Scholar]
  6. Burke J. M., Roberts C. W., Hunter C. A., Murray M., Alexander J. Temporal differences in the expression of mRNA for IL-10 and IFN-gamma in the brains and spleens of C57BL/10 mice infected with Toxoplasma gondii. Parasite Immunol. 1994 Jun;16(6):305–314. doi: 10.1111/j.1365-3024.1994.tb00353.x. [DOI] [PubMed] [Google Scholar]
  7. Heinzel F. P., Sadick M. D., Holaday B. J., Coffman R. L., Locksley R. M. Reciprocal expression of interferon gamma or interleukin 4 during the resolution or progression of murine leishmaniasis. Evidence for expansion of distinct helper T cell subsets. J Exp Med. 1989 Jan 1;169(1):59–72. doi: 10.1084/jem.169.1.59. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Heinzel F. P., Schoenhaut D. S., Rerko R. M., Rosser L. E., Gately M. K. Recombinant interleukin 12 cures mice infected with Leishmania major. J Exp Med. 1993 May 1;177(5):1505–1509. doi: 10.1084/jem.177.5.1505. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hunter C. A., Roberts C. W., Alexander J. Kinetics of cytokine mRNA production in the brains of mice with progressive toxoplasmic encephalitis. Eur J Immunol. 1992 Sep;22(9):2317–2322. doi: 10.1002/eji.1830220921. [DOI] [PubMed] [Google Scholar]
  10. Kaye P. M., Curry A. J., Blackwell J. M. Differential production of Th1- and Th2-derived cytokines does not determine the genetically controlled or vaccine-induced rate of cure in murine visceral leishmaniasis. J Immunol. 1991 Apr 15;146(8):2763–2770. [PubMed] [Google Scholar]
  11. Liew F. Y., O'Donnell C. A. Immunology of leishmaniasis. Adv Parasitol. 1993;32:161–259. doi: 10.1016/s0065-308x(08)60208-0. [DOI] [PubMed] [Google Scholar]
  12. Lynch N. R., Yarzábal L., Verde O., Avila J. L., Monzon H., Convit J. Delayed-type hypersensitivity and immunoglobulin E in American cutaneous leishmaniasis. Infect Immun. 1982 Dec;38(3):877–881. doi: 10.1128/iai.38.3.877-881.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Reed S. G., Scott P. T-cell and cytokine responses in leishmaniasis. Curr Opin Immunol. 1993 Aug;5(4):524–531. doi: 10.1016/0952-7915(93)90033-o. [DOI] [PubMed] [Google Scholar]
  14. Roberts M., Alexander J., Blackwell J. M. Genetic analysis of Leishmania mexicana infection in mice: single gene (Scl-2) controlled predisposition to cutaneous lesion development. J Immunogenet. 1990 Feb-Apr;17(1-2):89–100. doi: 10.1111/j.1744-313x.1990.tb00862.x. [DOI] [PubMed] [Google Scholar]
  15. Russell D. G., Xu S., Chakraborty P. Intracellular trafficking and the parasitophorous vacuole of Leishmania mexicana-infected macrophages. J Cell Sci. 1992 Dec;103(Pt 4):1193–1210. doi: 10.1242/jcs.103.4.1193. [DOI] [PubMed] [Google Scholar]

Articles from Immunology are provided here courtesy of British Society for Immunology

RESOURCES