Complement C2 receptor inhibitor trispanning confers an increased ability to resist complement-mediated lysis in Trypanosoma cruzi

Abstract

The ability to resist complement differs between the Y and ColombianaTrypanosoma cruzi strains. We found that the Y strain of T. cruziwas more able to resist the classical and lectin pathways of complement activation than the Colombiana strain. The complement C2 receptor inhibitor trispanning gene (CRIT) is highly conserved in both strains. At the protein level, CRIT is expressed only in stationary-phase epimastigotes of the Y but not the Colom-biana strain and is expressed in infectious metacyclic trypomastigotes of both strains. Y strain epimastigotes with an overexpressedCRITgene (pTEX-CRIT) had higher survival in normal human serum (NHS). Overexpression of the Y strain CRIT gene in Colombiana epimastigote forms increased the parasite’s resistance to lysis mediated by the classical and lectin pathways but not to lysis mediated by alternative pathways. CRIT involvement on the parasite surface was confirmed by showing that the lytic activity of NHS against epimastigotes could be restored by adding excess C2. Trypanosoma cruzi is a protozoan parasite that causes Chagas disease and that affects 18million people in Latin America, with 90 million at risk of infection worldwide [1]. Approximately 30%of individuals in the indetermi-nate stage, in which parasitemia is undetectable and pa