Parasitology Research

, Volume 82, Issue 5, pp 385–391 | Cite as

Production of interleukin 10 during malaria caused by lethal and nonlethal variants of Plasmodium yoelii yoelii

  • Fumie Kobayashi
  • Tsutomu Morii
  • Toshihiro Matsui
  • Takashi Fujino
  • Moriyasu Tsuji
  • Yoshihiko Watanabe
  • William P. Weidanz
Original Paper

Abstract

We investigated the induction of T-helper cell subsets during the course of lethal or nonlethal blood-stage Plasmodium yoelii 17X infection in C57BL/6 mice, which are relatively susceptible to these intraerythrocytic parasites. C57BL/6 mice infected with the nonlethal variant (PyNL) showed a moderate level of parasitemia and resolution of primary acute infection by week 4. Mice infected with the lethal variant (PyL) developed fulminating parasitemia and ultimately died. T-helper subset function was assessed during infection by determining the kinetics of in vitro production of the Thl-derived cytokine interferon-γ (IFN-γ) and the Th2-derived cytokine interleukin 10 (IL-10) by means of bioassay and enzyme-linked immunosorbent assay (ELISA), respectively. Spleen cells obtained from mice infected with PyL within the 1st week of infection produced high levels of IL-10 and IFN-γ in response to malaria antigen. IL-10 also appeared in sera from PyL-infected mice at the same time at which the in vitro IL-10 response peaked. In contrast, spleen cells from mice infected with PyNL failed to produce IL-10 during the course of infection. CD4+ T-lymphocytes from mice infected with the lethal variant were a major source of IL-10, although non T-cells were also involved in the production of IL-10 during this malaria infection. In addition, the initial burst of IL-10 in response to malaria antigens was seen concomitantly with the production of IFN-γ within the 1st week of infection. These results indicate that both Thl and Th2 subsets of T-helper lymphocytes are activated during infection with the lethal variant of P. yoelii and support the contention of other investigators that a strong Th2 response early in infection is associated with the lethal outcome of malaria.

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References

  1. Bienzle U, Fritsch KG, Hoth G, Rozdzinski E, Kohler K, Kalinowski M, Kremser P, Rosenkaimer F, Feldmeier H (1988) Inhibition of Plasmodium vinckei-malaria in mice by recombinant murine interferon-γ. Acta Trop (Basel) 45:289–290Google Scholar
  2. Bogdan C, Vodovotz Y, Nathan C (1991) Macrophage deactivation by interleukin 10. J Exp Med 174:1549–1555PubMedCrossRefGoogle Scholar
  3. Clark IA, Hunt NH, Butcher GA, Cowden WB (1987) Inhibition of murine malaria (Plasmodium chabaudi) in vivo by recombinant interferon-γ or tumor necrosis factor, and its enhancement by butylated hydroxyanisole. J Immunol 139:3493–3496PubMedGoogle Scholar
  4. Coffman RL (1982) Surface antigen expression and immunoglobulin gene rearrangement during mouse pre-B cell development. Immunol Rev 69:5–23PubMedCrossRefGoogle Scholar
  5. Diaynas DP, Quan ZS, Wall KA, Pierres A, Quintas J, Loken MR, Pierres M, Fitch FW (1983) Characterization of the murine T cell surface molecule, designated L3T4, identified by monoclonal antibody GK 1.5: similarity of L3T4 to the human Leu-3/T4 molecule. J Immunol 131:2445–2451Google Scholar
  6. Fiorentino DF, Bond MW, Mosmann TR (1989) Two types of mouse T helper cells. IV. Th2 clones secrete a factor that inhibits cytokine production by Thl clones. J Exp Med 170: 2081–2095PubMedCrossRefGoogle Scholar
  7. Fiorentino DF, Zlotnik A, Vieira P, Mosmann TR, Howard M, Moore KW, O’Garra A (1991a) IL-10 acts on the antigen-presenting cell to inhibit cytokine production by Thl cells. J Immunol 146:3444–3451Google Scholar
  8. Fiorentino DF, Zlotnik A, Mosmann TR, Howard M, O’Garra A (1991b) IL-10 inhibits cytokine production by activated macrophages. J Immunol 147:3815–3822Google Scholar
  9. Gazzinelli RT, Oswald IP, James SL, Sher A (1992) IL-10 inhibits parasite killing and nitrogen oxide production by IFN-γ activated macrophages. J Immunol 148:1792–1796PubMedGoogle Scholar
  10. Heinzel FP, Sadick MD, Mutha SS, Locksley RM (1991) Production of interferon γ, interleukin 2, interleukin 4, and interleukin 10 by CD4+ lymphocytes in vivo during healing and progressive murine leishmaniasis. Proc Natl Acad Sci USA 88:7011–7015PubMedCrossRefGoogle Scholar
  11. Langhorne J, Meding SJ, Eichmann K, Gillard SS (1989) The response of CD+ T cells to Plasmodium chabaudi chabaudi. Immunol Rev 112:71–94PubMedCrossRefGoogle Scholar
  12. Leo O, Foo M, Sachs DH, Samelson LE, Bluestone JA (1987) Identification of a monoclonal antibody specific for a murine T3 polypeptide. Proc Natl Acad Sci USA 84:1374–1378PubMedCrossRefGoogle Scholar
  13. Meding SJ, Cheng SC, Simon-Haarhaus B, Langhorne J (1990) Role of endogenous gamma interferon during infection with Plasmodium chabaudi chabaudi. Infect Immun 58:3671–3678PubMedGoogle Scholar
  14. Mellouk S, Green SJ, Nacy CA, Hoffman SL (1991) IFN-γ inhibits development of Plasmodium berghei exoerythrocytic stages in hepatocyte by an L-arginine-dependent effector mechanism. J Immunol 146:3971–3976PubMedGoogle Scholar
  15. Moore KW, Vieira P, Fiorentino DF, Trounstine ML, Kahn TA, Mosmann TR (1990) Homology of cytokine synthesis inhibitory factor (IL-10) to the Epstein-Barr virus gene BCRFI. Science 248:1230–1234PubMedCrossRefGoogle Scholar
  16. Moore KW, O’Garra A, Waal-Malefyt R de, Vieira P, Mosmann TR (1993) Interleukin-10. Annu Rev Immunol 11:165–190PubMedCrossRefGoogle Scholar
  17. Mosmann TR, Moore KW (1991) The role of IL-10 in cross-regulation of TH1 and TH2 responses. In: Ash C, Gallagher RB (eds) Immunoparasitology today. Elsevier Trends Journals, Cambridge, pp A49-A53Google Scholar
  18. Mosmann TR, Schumacher JH, Fiorentino DF, Leverah J, Moore KW, Bond MW (1990) Isolation of monoclonal antibodies specific for IL-4, IL-5, IL-6, and a new Th2-specific cytokine (IL-10), cytokine synthesis inhibitory factor, by using a solid phase radioimmunoadsorbent assay. J Immunol 145:2938–2945PubMedGoogle Scholar
  19. Nüssler A, Drapier JC, Renia L, Pied S, Miltgen F, Genrilini M, Mazier D (1991) L-Arginine-dependent destruction of intrahepatic malaria parasites in response to tumor necrosis factor and/or interleukin 6 stimulation. Eur J Immunol 21:227–230PubMedCrossRefGoogle Scholar
  20. O’Garra A, Stapleton G, Vinneta D, Pearce M, Schumacher J, Rugo H, Barbis D, Stall A, Cupp J, Moore K, Vieira P, Mosmann TR, Whitmore A, Arnold L, Haughton G, Howard M (1990) Production of cytokines by mouse B cells: B lymphomas and normal B cells produce interleukin 10. Int Immunol 2:821–832PubMedCrossRefGoogle Scholar
  21. O’Garra A, Chang R, Go N, Hasting M (1992) Ly-1 B (B-1) cells are the main source of B-cell-derived IL-10. Eur J Immunol 22:711–717PubMedCrossRefGoogle Scholar
  22. Peyron F, Burdin N, Ringwald P, Vuillez JP, Rousset F, Banchereau J (1994) High levels of circulating IL-10 in human malaria. Clin Exp Immunol 95:300–303PubMedGoogle Scholar
  23. Reed SG, Brownell CE, Russo DM, Silva JS, Grabstein KH, Morrissey PJ (1994) IL-10 mediates susceptibility to Trypanosoma cruzi infection. J Immunol 153:3135–3140PubMedGoogle Scholar
  24. Rockett KA, Awburn MM, Cowden WB, Clark IA (1991) Killing of Plasmodium falciparum in vitro by nitric oxide derivatives. Infect Immun 59:3280–3283PubMedGoogle Scholar
  25. Sarimiento M, Glasebrook AL, Fitch FW (1980) IgG or IgM monoclonal antibodies reactive with different determinants on the molecular complex bearing Lyt 2 antigen block T cell mediated cytolysis in the absence of complement. J Immunol 125:2665–2672Google Scholar
  26. Shear HL, Srinivasan R, Nolan T, Ng C (1989) Role of IFN-γ in lethal and nonlethal malaria in susceptible and resistant murine host. J Immunol 143:2038–2044PubMedGoogle Scholar
  27. Sher A, Fiorentino D, Caspar P, Pearce E, Mosmann TR (1991) Production of IL-10 by CD4+ T lymphocytes correlates with down-regulation of Thl cytokine synthesis in helminth infection. J Immunol 147:2713–2716PubMedGoogle Scholar
  28. Silva JS, Morrissey PJ, Grabstein KH, Mohler KM, Anderson D, Reed SG (1992) Interleukin-10 and interferon-y regulation of experimental Trypanosoma cruzi infection. J Exp Med 175:169–174PubMedCrossRefGoogle Scholar
  29. Slade SJ, Langhorne J (1989) Production of interferon-gamma during infection of mice with Plasmodium chabaudi chabaudi. Immunobiology 179:353–365PubMedGoogle Scholar
  30. Spitalny GL, Havell EA (1984) Monoclonal antibody to murine gamma interferon inhibits lymphokine-induced antiviral and macrophage tumoricidal activities. J Exp Med 159:1560–1565PubMedCrossRefGoogle Scholar
  31. Stevenson MM, Tarn M (1993) Differential induction of helper T cell subsets during blood-stage Plasmodium chabaudi AS infection in resistant and susceptible mice. Clin Exp Immunol 92:77–83PubMedGoogle Scholar
  32. Stevenson MM, Tam M, Nowotarski M (1990a) Role of interferon-γ and tumor necrosis factor in host resistance to Plasmodium chabaudi AS. Immunol Lett 25:115–122CrossRefGoogle Scholar
  33. Stevenson MM, Tam M, Belosevic M, Van Der Meide PH, Podoba JE (1990b) Role of endogenous gamma interferon in host response to infection with blood-stage Plasmodium chabaudi AS. Infect Immun 58:3225–3232Google Scholar
  34. Taylor-Robinson AW, Phillips RS (1994) B cells are required for the switch from Thl-to Th2-regulated immune responses to Plasmodium chabaudi chabaudi infection. Infect Immun 62:2490–2498PubMedGoogle Scholar
  35. Taylor-Robinson AW, Phillips RS, Severn A, Moncada S, Liew FY (1993) The role of Thl and Th2 cells in a rodent malaria infection. Science 260:1931–1934PubMedCrossRefGoogle Scholar
  36. Unanue ER (1984) Antigen-presenting function of the macrophage. Annu Rev Immunol 2:395–428PubMedCrossRefGoogle Scholar
  37. Waal Malefyt R de, Abras J, Bennet B, Figdor CG, Vries JE de (1991) Interleukin-10 (IL-10) inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes. J Exp Med 174:1209–1220CrossRefGoogle Scholar
  38. Waki S, Uehara S, Kanbe K, Ono K, Suzuki M, Nariuchi H (1992) The role of T cells in pathogenesis and protective immunity to murine malaria. Immunology 75:646–651PubMedGoogle Scholar
  39. Watier H, Pancre V, Lando D, Capron A, Auriault C (1993) IFN-γ treatment of rodents infected with erythrocytic stages of Plasmodium chabaudi: differential effects according to the immunological status. Int J Immunopharmacol 15:293–299PubMedCrossRefGoogle Scholar
  40. Weidanz WP, Long CA (1988) The role of T cells in immunity to malaria. Prog Allergy 41:215–252PubMedGoogle Scholar
  41. Wenisch C, Parschalk B, Narzt E, Looareesuwan S, Graninger W (1995) Elevated serum levels of IL-10 and IFN-γ in patients with acute Plasmodium falciparum malaria. Clin Immunol Immunopathol 74:115–117PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 1996

Authors and Affiliations

  • Fumie Kobayashi
    • 1
  • Tsutomu Morii
    • 1
  • Toshihiro Matsui
    • 1
  • Takashi Fujino
    • 1
  • Moriyasu Tsuji
    • 1
  • Yoshihiko Watanabe
    • 2
  • William P. Weidanz
    • 3
  1. 1.Department of Tropical Diseases and ParasitologyKyorin University School of MedicineMitaka, TokyoJapan
  2. 2.Faculty of Pharmaceutical SciencesKyoto UniversityKyotoJapan
  3. 3.Department of Medical Microbiology and ImmunologyUniversity of WisconsinMadisonUSA

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