Skip to main content
PMC home page
Infection and Immunity logoLink to Infection and Immunity
. 1997 Dec;65(12):4978–4983. doi: 10.1128/iai.65.12.4978-4983.1997

Progression of visceral leishmaniasis due to Leishmania infantum in BALB/c mice is markedly slowed by prior infection with Trichinella spiralis.

D Rousseau 1, Y Le Fichoux 1, X Stien 1, I Suffia 1, B Ferrua 1, J Kubar 1
PMCID: PMC175718  PMID: 9393785

Abstract

We investigated in BALB/c mice the influence of the immunological environment created by the nematode Trichinella spiralis on the course of visceral leishmaniasis due to Leishmania infantum. On the day of Leishmania inoculation (day 0), mice, T. spiralis infected 7 days earlier, presented increased gamma interferon (IFN-gamma), interleukin-4 (IL-4), and IL-5 mRNA levels locally and systemically and increased the potential of spleen cells to synthesize IFN-gamma and IL-4 after activation in vitro. Eighteen days after Leishmania inoculation (day 18), corresponding to the acute phase of leishmaniasis, the hepatic amastigote burden in mice coinfected with L. infantum and T. spiralis (LT mice) was significantly lower (P < 0.001) than that in mice infected with L. infantum only (L mice). IFN-gamma and IL-4 mRNAs were overexpressed in livers of LT and L mice. On day 70, corresponding to the chronic phase, the splenic amastigote load was significantly lower (P = 0.004) in LT mice than it was in L mice. Splenic IFN-gamma transcripts were overexpressed in both L and LT mice. After Leishmania-specific in vitro stimulation, cytokine production was enhanced in both groups, but spleen cells from L mice produced significantly more IFN-gamma than did spleen cells from LT mice. Our data (i) generalize previous results indicating the lack of a clear-cut correlation between the outcome of murine visceral leishmaniasis and the type of cytokine pattern and (ii) demonstrate that in LT mice, leishmaniasis takes a markedly milder course than it does in L mice, providing information on the potential consequences of coinfection in a mammalian host.

Full Text

The Full Text of this article is available as a PDF (193.9 KB).

Selected References

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

  1. Bell R. G. IgE, allergies and helminth parasites: a new perspective on an old conundrum. Immunol Cell Biol. 1996 Aug;74(4):337–345. doi: 10.1038/icb.1996.60. [DOI] [PubMed] [Google Scholar]
  2. Belosevic M., Finbloom D. S., Van Der Meide P. H., Slayter M. V., Nacy C. A. Administration of monoclonal anti-IFN-gamma antibodies in vivo abrogates natural resistance of C3H/HeN mice to infection with Leishmania major. J Immunol. 1989 Jul 1;143(1):266–274. [PubMed] [Google Scholar]
  3. Finkelman F. D., Pearce E. J., Urban J. F., Jr, Sher A. Regulation and biological function of helminth-induced cytokine responses. Immunol Today. 1991 Mar;12(3):A62–A66. doi: 10.1016/S0167-5699(05)80018-0. [DOI] [PubMed] [Google Scholar]
  4. Frydas S., Karagouni E., Dotsika E., Reale M., Barbacane R. C., Vlemmas I., Anogianakis G., Trakatellis A., Conti P. Generation of TNF alpha, IFN gamma, IL-6, IL-4 and IL-10 in mouse serum from trichinellosis: effect of the anti-inflammatory compound 4-deoxypyridoxine (4-DPD). Immunol Lett. 1996 Mar;49(3):179–184. doi: 10.1016/0165-2478(96)02501-1. [DOI] [PubMed] [Google Scholar]
  5. 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]
  6. Heinzel F. P., Sadick M. D., Mutha S. S., Locksley R. M. Production of interferon gamma, interleukin 2, interleukin 4, and interleukin 10 by CD4+ lymphocytes in vivo during healing and progressive murine leishmaniasis. Proc Natl Acad Sci U S A. 1991 Aug 15;88(16):7011–7015. doi: 10.1073/pnas.88.16.7011. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Holaday B. J., Sadick M. D., Wang Z. E., Reiner S. L., Heinzel F. P., Parslow T. G., Locksley R. M. Reconstitution of Leishmania immunity in severe combined immunodeficient mice using Th1- and Th2-like cell lines. J Immunol. 1991 Sep 1;147(5):1653–1658. [PubMed] [Google Scholar]
  8. Jankovic D., Sher A. Initiation and regulation of CD4+ T-cell function in host-parasite models. Chem Immunol. 1996;63:51–65. [PubMed] [Google Scholar]
  9. 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]
  10. Kelly E. A., Cruz E. S., Hauda K. M., Wassom D. L. IFN-gamma- and IL-5-producing cells compartmentalize to different lymphoid organs in Trichinella spiralis-infected mice. J Immunol. 1991 Jul 1;147(1):306–311. [PubMed] [Google Scholar]
  11. Locksley R. M., Scott P. Helper T-cell subsets in mouse leishmaniasis: induction, expansion and effector function. Immunol Today. 1991 Mar;12(3):A58–A61. doi: 10.1016/S0167-5699(05)80017-9. [DOI] [PubMed] [Google Scholar]
  12. Miralles G. D., Stoeckle M. Y., McDermott D. F., Finkelman F. D., Murray H. W. Th1 and Th2 cell-associated cytokines in experimental visceral leishmaniasis. Infect Immun. 1994 Mar;62(3):1058–1063. doi: 10.1128/iai.62.3.1058-1063.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Moll H., Röllinghoff M. Resistance to murine cutaneous leishmaniasis is mediated by TH1 cells, but disease-promoting CD4+ cells are different from TH2 cells. Eur J Immunol. 1990 Sep;20(9):2067–2074. doi: 10.1002/eji.1830200927. [DOI] [PubMed] [Google Scholar]
  14. Morris L., Troutt A. B., McLeod K. S., Kelso A., Handman E., Aebischer T. Interleukin-4 but not gamma interferon production correlates with the severity of murine cutaneous leishmaniasis. Infect Immun. 1993 Aug;61(8):3459–3465. doi: 10.1128/iai.61.8.3459-3465.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Mosmann T. R., Sad S. The expanding universe of T-cell subsets: Th1, Th2 and more. Immunol Today. 1996 Mar;17(3):138–146. doi: 10.1016/0167-5699(96)80606-2. [DOI] [PubMed] [Google Scholar]
  16. Murray H. W., Cervia J. S., Hariprashad J., Taylor A. P., Stoeckle M. Y., Hockman H. Effect of granulocyte-macrophage colony-stimulating factor in experimental visceral leishmaniasis. J Clin Invest. 1995 Mar;95(3):1183–1192. doi: 10.1172/JCI117767. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Murray H. W., Hariprashad J., Coffman R. L. Behavior of visceral Leishmania donovani in an experimentally induced T helper cell 2 (Th2)-associated response model. J Exp Med. 1997 Mar 3;185(5):867–874. doi: 10.1084/jem.185.5.867. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Murray H. W., Hariprashad J. Interleukin 12 is effective treatment for an established systemic intracellular infection: experimental visceral leishmaniasis. J Exp Med. 1995 Jan 1;181(1):387–391. doi: 10.1084/jem.181.1.387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Murray H. W., Masur H., Keithly J. S. Cell-mediated immune response in experimental visceral leishmaniasis. I. Correlation between resistance to Leishmania donovani and lymphokine-generating capacity. J Immunol. 1982 Jul;129(1):344–350. [PubMed] [Google Scholar]
  20. Murray H. W., Miralles G. D., Stoeckle M. Y., McDermott D. F. Role and effect of IL-2 in experimental visceral leishmaniasis. J Immunol. 1993 Jul 15;151(2):929–938. [PubMed] [Google Scholar]
  21. Murray H. W., Squires K. E., Miralles C. D., Stoeckle M. Y., Granger A. M., Granelli-Piperno A., Bogdan C. Acquired resistance and granuloma formation in experimental visceral leishmaniasis. Differential T cell and lymphokine roles in initial versus established immunity. J Immunol. 1992 Mar 15;148(6):1858–1863. [PubMed] [Google Scholar]
  22. Murray H. W., Stern J. J., Welte K., Rubin B. Y., Carriero S. M., Nathan C. F. Experimental visceral leishmaniasis: production of interleukin 2 and interferon-gamma, tissue immune reaction, and response to treatment with interleukin 2 and interferon-gamma. J Immunol. 1987 Apr 1;138(7):2290–2297. [PubMed] [Google Scholar]
  23. Noben-Trauth N., Kropf P., Müller I. Susceptibility to Leishmania major infection in interleukin-4-deficient mice. Science. 1996 Feb 16;271(5251):987–990. doi: 10.1126/science.271.5251.987. [DOI] [PubMed] [Google Scholar]
  24. Ramaswamy K., Negrao-Correa D., Bell R. Local intestinal immune responses to infections with Trichinella spiralis. Real-time, continuous assay of cytokines in the intestinal (afferent) and efferent thoracic duct lymph of rats. J Immunol. 1996 Jun 1;156(11):4328–4337. [PubMed] [Google Scholar]
  25. 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]
  26. Reiner S. L., Locksley R. M. The regulation of immunity to Leishmania major. Annu Rev Immunol. 1995;13:151–177. doi: 10.1146/annurev.iy.13.040195.001055. [DOI] [PubMed] [Google Scholar]
  27. Sadick M. D., Locksley R. M., Tubbs C., Raff H. V. Murine cutaneous leishmaniasis: resistance correlates with the capacity to generate interferon-gamma in response to Leishmania antigens in vitro. J Immunol. 1986 Jan;136(2):655–661. [PubMed] [Google Scholar]
  28. Sadick M. D., Street N., Mosmann T. R., Locksley R. M. Cytokine regulation of murine leishmaniasis: interleukin 4 is not sufficient to mediate progressive disease in resistant C57BL/6 mice. Infect Immun. 1991 Dec;59(12):4710–4714. doi: 10.1128/iai.59.12.4710-4714.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Scott P., Eaton A., Gause W. C., di Zhou X., Hondowicz B. Early IL-4 production does not predict susceptibility to Leishmania major. Exp Parasitol. 1996 Nov;84(2):178–187. doi: 10.1006/expr.1996.0103. [DOI] [PubMed] [Google Scholar]
  30. Scott P. IFN-gamma modulates the early development of Th1 and Th2 responses in a murine model of cutaneous leishmaniasis. J Immunol. 1991 Nov 1;147(9):3149–3155. [PubMed] [Google Scholar]
  31. Sher A., Coffman R. L. Regulation of immunity to parasites by T cells and T cell-derived cytokines. Annu Rev Immunol. 1992;10:385–409. doi: 10.1146/annurev.iy.10.040192.002125. [DOI] [PubMed] [Google Scholar]
  32. Smelt S. C., Engwerda C. R., McCrossen M., Kaye P. M. Destruction of follicular dendritic cells during chronic visceral leishmaniasis. J Immunol. 1997 Apr 15;158(8):3813–3821. [PubMed] [Google Scholar]
  33. Stern J. J., Oca M. J., Rubin B. Y., Anderson S. L., Murray H. W. Role of L3T4+ and LyT-2+ cells in experimental visceral leishmaniasis. J Immunol. 1988 Jun 1;140(11):3971–3977. [PubMed] [Google Scholar]
  34. Suffia I., Quaranta J. F., Eulalio M. C., Ferrua B., Marty P., Le Fichoux Y., Kubar J. Human T-cell activation by 14- and 18-kilodalton nuclear proteins of Leishmania infantum. Infect Immun. 1995 Oct;63(10):3765–3771. doi: 10.1128/iai.63.10.3765-3771.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Swihart K., Fruth U., Messmer N., Hug K., Behin R., Huang S., Del Giudice G., Aguet M., Louis J. A. Mice from a genetically resistant background lacking the interferon gamma receptor are susceptible to infection with Leishmania major but mount a polarized T helper cell 1-type CD4+ T cell response. J Exp Med. 1995 Mar 1;181(3):961–971. doi: 10.1084/jem.181.3.961. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Tumang M. C., Keogh C., Moldawer L. L., Helfgott D. C., Teitelbaum R., Hariprashad J., Murray H. W. Role and effect of TNF-alpha in experimental visceral leishmaniasis. J Immunol. 1994 Jul 15;153(2):768–775. [PubMed] [Google Scholar]
  37. Urban J. F., Jr, Madden K. B., Svetić A., Cheever A., Trotta P. P., Gause W. C., Katona I. M., Finkelman F. D. The importance of Th2 cytokines in protective immunity to nematodes. Immunol Rev. 1992 Jun;127:205–220. doi: 10.1111/j.1600-065x.1992.tb01415.x. [DOI] [PubMed] [Google Scholar]
  38. Vercelli D., Jabara H. H., Lee B. W., Woodland N., Geha R. S., Leung D. Y. Human recombinant interleukin 4 induces Fc epsilon R2/CD23 on normal human monocytes. J Exp Med. 1988 Apr 1;167(4):1406–1416. doi: 10.1084/jem.167.4.1406. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Vouldoukis I., Riveros-Moreno V., Dugas B., Ouaaz F., Bécherel P., Debré P., Moncada S., Mossalayi M. D. The killing of Leishmania major by human macrophages is mediated by nitric oxide induced after ligation of the Fc epsilon RII/CD23 surface antigen. Proc Natl Acad Sci U S A. 1995 Aug 15;92(17):7804–7808. doi: 10.1073/pnas.92.17.7804. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Wilson M. E., Sandor M., Blum A. M., Young B. M., Metwali A., Elliott D., Lynch R. G., Weinstock J. V. Local suppression of IFN-gamma in hepatic granulomas correlates with tissue-specific replication of Leishmania chagasi. J Immunol. 1996 Mar 15;156(6):2231–2239. [PubMed] [Google Scholar]
  41. Zwingenberger K., Harms G., Pedrosa C., Omena S., Sandkamp B., Neifer S. Determinants of the immune response in visceral leishmaniasis: evidence for predominance of endogenous interleukin 4 over interferon-gamma production. Clin Immunol Immunopathol. 1990 Nov;57(2):242–249. doi: 10.1016/0090-1229(90)90038-r. [DOI] [PubMed] [Google Scholar]

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

RESOURCES