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  • The EMBO Journal (2000) 19, 1476 - 1485
  • doi:10.1093/emboj/19.7.1476

Highly purified glycosylphosphatidylinositols from Trypanosoma cruzi are potent proinflammatory agents

Igor C. Almeida1,2, Maristela M. Camargo3, Daniela O. Procópio3, Luiz S. Silva4, Angela Mehlert1, Luiz R. Travassos4, Ricardo T. Gazzinelli5 and Michael A.J. Ferguson1

  1. Division of Molecular Parasitology and Biological Chemistry, Department of Biochemistry, University of Dundee, Dundee DD1 5EH, UK
  2. Present address: Department of Parasitology, Biomedical Sciences Institute, Universidade de São Paulo, SP 05508-900, Brazil
  3. Department of Biochemistry and Immunology, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
  4. Discipline of Cell Biology, Department of Microbiology, Immunology and Parasitology, Universidade Federal de São Paulo, São Paulo, SP 0423-062, Brazil
  5. Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, MG 30190-002, Brazil

Correspondence to:

Michael A.J. Ferguson, E-mail: m.a.j.ferguson@dundee.ac.uk

Received 26 October 1999; Accepted 3 February 2000; Revised 3 February 2000

Intracellular protozoan parasites are potent stimulators of cell-mediated immunity. The induction of macrophage proinflammatory cytokines by Trypanosoma cruzi is considered to be important in controlling the infection and the outcome of Chagas' disease. Here we show that the potent tumour necrosis factor-alpha-, interleukin-12- and nitric oxide-inducing activities of T.cruzi trypomastigote mucins were recovered quantitatively in a highly purified and characterized glycosylphosphatidylinositol (GPI) anchor fraction of this material. The bioactive trypomastigote GPI fraction was compared with a relatively inactive GPI fraction prepared from T.cruzi epimastigote mucins. The trypomastigote GPI structures were found to contain additional galactose residues and unsaturated, instead of saturated, fatty acids in the sn-2 position of the alkylacylglycerolipid component. The latter feature is essential for the extreme potency of the trypomastigote GPI fraction, which is at least as active as bacterial endotoxin and Mycoplasma lipopeptide and, therefore, one of the most potent microbial proinflammatory agents known.

  • Keywords:

    • Chagas' disease,
    • cytokines,
    • glycosylphosphatidylinositol,
    • inflammation,
    • nitric oxide