Parasitology Research

, Volume 94, Issue 3, pp 207–212 | Cite as

Immune response induced by New World Leishmania species in C57BL/6 mice

  • Tatiani Uceli Maioli
  • Erica Takane
  • Rosa Maria Esteves Arantes
  • Juliana Lopes Rangel Fietto
  • Luís Carlos Crocco Afonso
Original Paper

Abstract

In the present study, C57BL/6 mice were inoculated with metacyclic Leishmania amazonensis or L. braziliensis promastigotes. While these animals were capable of controlling the infection by L. braziliensis, they developed chronic lesions with elevated numbers of parasites when infected by L. amazonensis. The differences in parasite control were associated with a decreased production of IFN-γ and TNF by lymph node cells from L. amazonensis-infected mice. Furthermore, these animals presented decreased spleen cell proliferation and activation of germinal centers. In addition, we compared the ability of these parasites to hydrolyze extracellular ATP and AMP. While the ATPase activity of both parasite species was similar, L. amazonensis promastigotes presented higher AMP hydrolytic activity. This increased activity may lead to an increased production of adenosine, which has been shown to present anti-inflammatory activity and may thus be involved in the establishment of the immunosuppression observed in mice infected by L. amazonensis.

Notes

Acknowledgements

This study received financial support from CAPES and was performed in accordance with Brazilian law.

References

  1. Afonso LCC, Scott P (1993) Immune responses associated with susceptibility of C57BL/10 mice to Leishmania amazonensis. Infect Immun 61:2952–2959PubMedGoogle Scholar
  2. Berredo-Pinho M, Peres-Sampaio CE, Chrispim PP, Belmont-Firpo R, Lemos AP, Martiny A, Vannier-Santos MA, Meyer-Fernandes JR (2001) A Mg-dependent ecto-ATPase in Leishmania amazonensis and its possible role in adenosine acquisition and virulence. Arch Biochem Biophys 391:16–24CrossRefPubMedGoogle Scholar
  3. Carvalho EM, Correia FD, Bacellar O, Almeida RP, Lessa H, Rocha H (1995) Characterization of the immune response in subjects with self-healing cutaneous leishmaniasis. Am J Trop Med Hyg 53:273–277PubMedGoogle Scholar
  4. Childs GE, Lightner LK, McKinney L, Groves MG, Price EE, Hendricks LD (1984) Inbred mice as model hosts for cutaneous leishmaniasis. I. Resistance and susceptibility to infection with Leishmania braziliensis, L. mexicana, and L. aethiopica. Ann Trop Med Parasitol 78:25–34PubMedGoogle Scholar
  5. Coimbra ES, Gonçalves-da-Costa SC, Corte-Real S, De Freitas FG, Durão AC, Souza CS, Silva-Santos MI, Vasconcelos EG (2002) Characterization and cytochemical localization of an ATP diphosphohydrolase from Leishmania amazonensis promastigotes. Parasitology 124:137–143CrossRefPubMedGoogle Scholar
  6. Convit J, Pinardi ME, Rondón AJ (1972) Diffuse cutaneous leishmaniasis: a disease due to an immunological defect in the host. Trans R Soc Trop Med Hyg 66:603–610CrossRefPubMedGoogle Scholar
  7. Coutinho SG, Cruz AM da, Bertho AL, Santiago MA, De-Luca P (1998) Immunologic patterns associated with cure in human American cutaneous leishmaniasis. Braz J Med Biol Res 31:139–142PubMedGoogle Scholar
  8. da Cruz AM, Machado ES, Menezes JA, Rutowitsch MS, Coutinho SG (1992) Cellular and humoral immune responses of a patient with American cutaneous leishmaniasis and AIDS. Trans R Soc Trop Med Hyg 86:511–512CrossRefPubMedGoogle Scholar
  9. DeKrey GK, Lima HC, Titus RG (1998) Analysis of the immune responses of mice to infection with Leishmania braziliensis. Infect Immun 66:827–829PubMedGoogle Scholar
  10. Fietto JL, DeMarco R, Nascimento IP, Castro IM, Carvalho TM, De Souza W, Bahia MT, Alves MJ, Verjovski-Almeida S (2004) Characterization and immunolocalization of an NTP diphosphohydrolase of Trypanosoma cruzi. Biochem Biophys Res Commun 316:454–460Google Scholar
  11. Goding JW, Howard MC (1998) Ecto-enzymes of lymphoid cells. Immunol Rev 161:5–10Google Scholar
  12. Heinzel FP, Sadick MD, Holaday BJ, Coffman RL, Locksley RM (1989) Reciprocal expression of interferon gamma or IL4 during the resolution or progression of murine leishmaniasis. Evidence for expansion of distinct helper T cell subsets. J Exp Med 169:59–72CrossRefPubMedGoogle Scholar
  13. Ji J, Sun J, Soong L (2003) Impaired expression of inflammatory cytokines and chemokines at early stages of infection with Leishmania amazonensis. Infect Immun 71:4278–4288CrossRefPubMedGoogle Scholar
  14. La Sala A, Ferrari D, Di Virgilio F, Idzko M, Norgauer J, Girolomoni G (2003) Alerting and tuning the immune response by extracellular nucleotides. J Leukoc Biol 73:339–343CrossRefPubMedGoogle Scholar
  15. Lattime SC, Stopacciaro A, Stutman O (1988) Limiting dilution analysis of TNF producing cells in C3H/HeJ mice. J Immunol 141:3422–3428PubMedGoogle Scholar
  16. Lima HC, Titus RG (1996) Effects of sand fly vector saliva on development of cutaneous lesions and the immune response to Leishmania braziliensis in BALB/c mice. Infect Immun 64:5442–5445PubMedGoogle Scholar
  17. Lima HC, DeKrey GK, Titus RG (1999) Resolution of an infection with Leishmania braziliensis confers complete protection to a subsequent challenge with Leishmania major in BALB/c mice. Mem Inst Oswaldo Cruz 94:71–76Google Scholar
  18. Locksley RM, Heinzel FP, Sadick MD, Holaday BJ, Gardner KD Jr (1987) Murine cutaneous leishmaniasis: susceptibility correlates with differential expansion of helper T-cells subsets. Ann Inst Pasteur Paris 138:744–749Google Scholar
  19. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the folin phenol reagent. J Biol Chem 193:265–275PubMedGoogle Scholar
  20. Marcus AJ, Broekman MJ, Drosopoulos JH, Islam N, Pinsky DJ, Sesti C, Levi R (2003) Metabolic control of excessive extracellular nucleotide accumulation by CD39/ecto-nucleotidase-1: implications for ischemic vascular diseases. J Pharmacol Exp Ther 305:9–16CrossRefPubMedGoogle Scholar
  21. Mattner F, Magram J, Ferrante J, Launois P, Di Padova K, Behin R, Gately MK, Louis JA, Alber G (1996) Genetically resistant mice lacking interleukin-12 are susceptible to infection with Leishmania major and mount a polarized Th2 cell response. Eur J Immunol 26:1553–1559PubMedGoogle Scholar
  22. Mattner F, Di Padova K, Alber G (1997) Interleukin-12 is indispensable for protective immunity against Leishmania major. Infect Immun 65:4378–4383PubMedGoogle Scholar
  23. Mizumoto N, Kumamoto T, Robson SC, Sevigny J, Matsue H, Enjyoji K, Takashima A (2002) CD39 is the dominant Langerhans cell-associated ecto-NTPDase: modulatory roles in inflammation and immune responsiveness. Nat Med 8:358–365CrossRefPubMedGoogle Scholar
  24. Moll H, Röllinghoff M (1990) Resistance to murine cutaneous leishmaniasis is mediated by TH1 cells, but disease-promoting CD4+ cells are different from TH2 cells. Eur J Immunol 20:2067-2074PubMedGoogle Scholar
  25. Sacks D, Noben-Trauth N (2002) The immunology of susceptibility and resistance to Leishmania major in mice. Nat Rev Immunol 2:845–858CrossRefPubMedGoogle Scholar
  26. Sartori A, Oliveira MA, Scott P, Trinchieri G (1997) Metacyclogenesis modulates the ability of Leishmania promastigotes to induce IL-12 production in human mononuclear cells. J Immunol 159:2849–2857PubMedGoogle Scholar
  27. Scharton-Kersten T, Scott P (1995) The role of the innate immune response in Th1 cell development following Leishmania major infection. J Leukoc Biol 57:515–522PubMedGoogle Scholar
  28. Scott P (1989) The role of TH1 and TH2 cells in experimental cutaneous leishmaniasis. Exp Parasitol 68:369–372CrossRefPubMedGoogle Scholar
  29. Scott P (1991) IFN-γ modulates the early development of Th1 and Th2 responses in a murine model of cutaneous leishmaniasis. J Immunol 147:3149–3155PubMedGoogle Scholar
  30. Soong L, Xu J-C, Grewal IS, P. K, Sun J, McMahon-Pratt D, Flavell RA (1996) Disruption of CD40-CD40 ligand interactions results in enhanced susceptibility to Leishmania amazonensis infection. Immunity 4:263–273CrossRefPubMedGoogle Scholar
  31. Späth GF, Beverley SM (2001) A lipophosphoglycan-independent method for isolation of infective Leishmania metacyclic promastigotes by density gradient centrifugation. Exp Parasitol 99:97–103CrossRefPubMedGoogle Scholar
  32. Taussky HH, Shorr E (1953) A microcolorimetric method for the determination of inorganic phosphorus. J Biol Chem 202:675–685PubMedGoogle Scholar
  33. Toledo V, Mayrink W, Gollob K, Oliveira M, Costa C, Genaro O, Pinto J, Afonso L (2001) Immunochemotherapy in American cutaneous leishmaniasis: immunological aspects before and after treatment. Mem Inst Oswaldo Cruz 96:89–98Google Scholar
  34. Wilhelm P, Ritter U, Labbow S, Donhauser N, Rollinghoff M, Bogdan C, Korner H (2001) Rapidly fatal leishmaniasis in resistant C57BL/6 mice lacking TNF. J Immunol 166:4012–4019PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Tatiani Uceli Maioli
    • 1
  • Erica Takane
    • 1
  • Rosa Maria Esteves Arantes
    • 2
  • Juliana Lopes Rangel Fietto
    • 1
  • Luís Carlos Crocco Afonso
    • 1
  1. 1.Departamento de Ciências Biológicas, Instituto de Ciências Exatas e Biológicas/NUPEBUniversidade Federal de Ouro PretoOuro PretoBrazil
  2. 2.Departamento de PatologiaUniversidade Federal de Minas GeraisBelo HorizonteBrazil

Personalised recommendations