Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Trypanosoma brucei is protected from the cytostatic effects of nitric oxide under in vivo conditions

Abstract

In mice infected withTrypanosoma brucei, splenic and peritoneal macrophages release substantial amounts of nitric oxide (NO). The production of NO by activated macrophages has been reported to be a nonspecific immune-effector mechansism against several parasites, and in this work we investigate the role of NO in killingT. brucei. Addition of bloodstream trypanosomes to peritoneal macrophages activated in vitro resulted in an NO-dependent inhibition of parasite growth. This effect was totally abrogated when dilutions of whole blood were included in the cultures, suggesting that bloodstream parasites such asT. brucei are not susceptible to NO-mediated killing in vivo.

This is a preview of subscription content, log in to check access.

References

  1. Adams LB, Hibbs JB, Taintor RR, Krohenbuhl JL (1990) Microbiostatic effect of murine-activated macrophages forToxoplasma gondii. J Immunol 144:2725–2729

  2. Anthony LSD, Morrissey PJ, Nano FE (1992) Growth inhibition ofFrancisella tularensis live vaccine strain by IFN—activated macrophages is mediated by reactive nitrogen intermediates derived froml-arginine metabolism. J Immunol 148:1829–1834

  3. Askonas BA (1985) Macrophages as mediators of immunosuppression in murine African trypanosomiasis. Curr Top Microbiol Immunol 117:119–127

  4. Baltz T, Baltz D, Giroud C, Crockett J (1985) Cultivation in a semidefined medium of animal infective forms ofTrypanosoma brucei, T. equiperdum, T. evansi, T. rhodiense andT. gambiense. EMBO J 4:1273–1277

  5. Barry JD, Crowe JS, Vickerman K (1983) Instability of theTrypanosoma brucei rhodesiense metacyclic variable antigen repertoire. Nature 306:699–701

  6. Beckerman KP, Rogers HW, Corbett JA, Schreiber RD, McDaniel ML, Unanue ER (1993) Release of nitric oxide during T-cell-independent pathway of macrophage activation. J Immunol 150:888–895

  7. Borst P (1986) Discontinuous transcription and antigenic variation in trypanosomes. Annu Rev Biochem 55:701–732

  8. Chan J, Xing Y, Magliozzo RS, Bloom BR (1992) Killing of virulentMycobacterium tuberculosis by reactive nitrogen intermediates produced by activated macrophages. J Exp Med 175:1111–1122

  9. Darji A, Sileghem M, Heremans H, Brys L, De Baetselier P (1993) Inhibition of T-cell responsiveness during experimental infections withTrypanosoma brucei: active involvement of endogenous gamma interferon. Infect Immun 61:3098–3102

  10. Ding AH, Nathan CF, Stuehr DJ (1988) Release of reactive nitrogen intermediates and reactive oxygen intermediates from mouse peritoneal macrophages. J Immunol 141:2407–2412

  11. Doyle JJ, Hirumi H, Hirumi K, Lupton EN, Cross GAM (1980) Antigenic variation in clones of animal infectiveT. brucei derived and maintained in vitro. Parasitology 80:359–369

  12. Feelisch M, Noack EA (1987) Correlation between nitric oxide formation during degradation of organic nitrates and activation of guanylate cyclase. Eur J Pharmacol 139:19–30

  13. Ignarro LJ (1990) Biosynthesis and metabolism of endotheliumderived nitric oxide. Annu Rev Pharmacol Toxicol 30:535–560

  14. James SL, Glaven J (1989) Macrophage cytotoxicity against schistosomula ofSchistosoma mansoni involves arginine-dependent production of reactive nitrogen intermediates. J Immunol 143:4208–4212

  15. Liew FY (1993) The role of nitric oxide in parasitic diseases. Ann Trop Med Parasitol 87:637–642

  16. Liew FY, Millot S, Parkinson C, Palmer RMJ, Moncada S (1990) Macrophage killing ofLeishmania parasite in vivo is mediated by nitric oxide froml-arginine. J Immunol 144:4794–4797

  17. Mills CD (1991) Molecular basis of suppressor macrophages. J Immunol 146:2719–2723

  18. Severn A, Xu D, Doyle J, Leal LMC, O'Donnell CA, Brett SJ, Moss DW, Liew FY (1993) Pre-exposure of murine macrophages to lipopolysaccharide inhibits the induction of nitric oxide synthase and reduces leishmanicidal activity. Eur J Immunol 23:1711–1714

  19. Sternberg J, McGuigan F (1992) Nitric oxide mediates suppression of T-cell responses in murineTrypanosoma brucei infection. Eur J Immunol 22:2741–2744

  20. Summersgill JT, Powell LA, Buster BL, Miller RD, Ramirez JA (1992) Killing ofLegionella pneumophila by nitric oxide in γ-interferons-activated macrophages. J Leukocyte Biol 52:625–629

  21. Van Meirvenne N, Janssen PG, Magnus E (1975) Antigenic variation in syringe passaged populations ofTrypanosoma (Trypanozoon) brucei. I. Rationalisation of the experimental approach. Ann Soc Belge Med Trop 55:1–23

  22. Vincendeau P, Daulouede S (1991) Macrophage cytostatic effect onTrypanosoma musculi involves anl-arginine-dependent mechanism. J Immunol 146:4338–4343

  23. Vincendeau P, Daulouede S, Veyret B, Darde ML, Bouteille B, Lemesre JL (1992) Nitric oxide-mediated cytostatic activity onTrypanosoma brucei gambiense andT. brucei brucei. Exp Parasitol 75:353–360

Download references

Author information

Correspondence to J. M. Sternberg.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Mabbott, N.A., Sutherland, I.A. & Sternberg, J.M. Trypanosoma brucei is protected from the cytostatic effects of nitric oxide under in vivo conditions. Parasitol Res 80, 687–690 (1994). https://doi.org/10.1007/BF00932954

Download citation

Keywords

  • Oxide
  • Nitric Oxide
  • Peritoneal Macrophage
  • Trypanosoma
  • Parasite Growth