The C2 receptor CRIT protects Trypanosoma cruzi against classical and MBL-directed, but not alternative pathway complement activation (51.14)

Abstract

Abstract We show that the sylvatic class I strains of Trypanosoma cruzi resist more effectively the classical (CP) and mannan-binding lectin (LP) mediated complement activation than the domestic class II strains. T. cruzi Colombiana (sylvatic class II) showed under 3% survival compared with 45% for the Y strain (domestic class I). The AP plays a minimal role in lysis mediated in the short-term. The complement C2 receptor CRIT gene is highly similar in T. cruzi class I and class II parasites. It is not expressed in log growth phase epimastigote insect forms of either class and is only expressed in late growth phase epimastigote (infective stage) forms of T. cruzi Y (class I ) but not Colombiana (class II) strains. When the Tc-CRIT gene of T. cruzi Y strain was overexpressed in Y and Colombiana strains, the transgenic parasites (pTEX-Tc-CRIT) showed 86% survival after 5 minutes in normal human serum (NHS) compared to 57.4 % (pTEX) and 53.4% (wild type). Once more in the presence of AP alone there was 80% survival after 5 and 10 minutes. As CRIT is a receptor which principally binds complement C2 it is presumed that overexpressed CRIT in epimastigote forms of T. cruzi Y strain resist CP and LP by depletion of C2 from NHS. Experiments in which an excess of C2 was added to NHS confirmed this mechanism by restoring hemolytic activity.