Alteration of macrophage function by a Trypanosoma cruzi membrane mucin

J Immunol. 1997 Nov 15;159(10):4983-9.

Abstract

Cytokines secreted by macrophages play important roles in the immune response to Trypanosoma cruzi. Here, we report that a purified glycosylphosphatidylinositol (GPI)-anchored mucin from the T. cruzi membrane, Ag C10, is able to bind to the macrophage cell surface and blocks the subsequent binding of mAb against CD62L/L-selectin, whereas binding of mAbs directed against other monocyte surface molecules is unaffected. In addition, Ag C10 binding to macrophages triggered a CD54/ICAM-1-mediated cell adhesion as well as an increase in intracellular Ca2+, which was further augmented by cross-linking the Ag C10-bound surface receptors by mAb against Ag C10. Interestingly, Ag C10-treated monocytes secreted IL-1beta, but not TNF-alpha or IL-12. Moreover, these cells could secrete IL-1beta, but not TNF-alpha or IL-12, after activation with LPS. T. cruzi-infected macrophages displayed similar alterations in cytokine secretion, with an impaired ability to secrete IL-12 and TNF-alpha, but not IL-1beta, upon LPS activation. These effects were substantially inhibited by neutralizing mAb against Ag C10. These effects appeared to take place at the transcriptional level, since mRNA for TNF-alpha, but not that for IL-1beta, was drastically reduced in LPS-stimulated infected cells treated with Ag C10. Conceivably, inhibition of TNF-alpha and IL-12 by T. cruzi could be involved in the evasion of the immune response by this parasite.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Protozoan / metabolism
  • Cell Line
  • Cell Membrane / immunology
  • Cell Membrane / metabolism
  • Cytokines / metabolism
  • Humans
  • Macrophages / immunology*
  • Macrophages / metabolism
  • Macrophages / parasitology*
  • Monocytes
  • Mucins / immunology
  • Mucins / pharmacology*
  • Protein Binding / immunology
  • Trypanosoma cruzi / chemistry
  • Trypanosoma cruzi / immunology*
  • Tumor Cells, Cultured

Substances

  • Antigens, Protozoan
  • Cytokines
  • Mucins