The classical activation pathway of the human complement system is specifically inhibited by calreticulin from Trypanosoma cruzi

J Immunol. 2004 Mar 1;172(5):3042-50. doi: 10.4049/jimmunol.172.5.3042.

Abstract

The high resistance of Trypanosoma cruzi trypomastigotes, the causal agent of Chagas' disease, to complement involves several parasite strategies. In these in vitro studies, we show that T. cruzi calreticulin (TcCRT) and two subfragments thereof (TcCRT S and TcCRT R domains) bind specifically to recognition subcomponents of the classical and lectin activation pathways (i.e., to collagenous tails of C1q and to mannan-binding lectin) of the human complement system. As a consequence of this binding, specific functional inhibition of the classical pathway and impaired mannan-binding lectin to mannose were observed. By flow cytometry, TcCRT was detected on the surface of viable trypomastigotes and, by confocal microscopy, colocalization of human C1q with surface TcCRT of infective trypomastigotes was visualized. Taken together, these findings imply that TcCRT may be a critical factor contributing to the ability of trypomastigotes to interfere at the earliest stages of complement activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding, Competitive / immunology
  • Calreticulin / metabolism
  • Calreticulin / physiology*
  • Collagen / metabolism
  • Complement C1q / antagonists & inhibitors
  • Complement C1q / metabolism
  • Complement Inactivator Proteins / metabolism
  • Complement Inactivator Proteins / physiology*
  • Complement Pathway, Classical / immunology*
  • Humans
  • Immunosuppressive Agents* / metabolism
  • Mannose / metabolism
  • Mannose-Binding Lectin / antagonists & inhibitors
  • Mannose-Binding Lectin / metabolism
  • Membrane Proteins / metabolism
  • Membrane Proteins / physiology
  • Microscopy, Confocal
  • Peptide Fragments / metabolism
  • Peptide Fragments / physiology
  • Protein Binding / immunology
  • Protein Structure, Tertiary
  • Trypanosoma cruzi / growth & development
  • Trypanosoma cruzi / immunology*
  • Trypanosoma cruzi / pathogenicity

Substances

  • Calreticulin
  • Complement Inactivator Proteins
  • Immunosuppressive Agents
  • Mannose-Binding Lectin
  • Membrane Proteins
  • Peptide Fragments
  • Complement C1q
  • Collagen
  • Mannose