Trypanosoma cruzi calreticulin inhibits the complement lectinpathway activation by direct interaction with L-Ficolin

Abstract

Trypanosoma cruzi, the agent of Chagas’ disease, the sixth neglected tropical disease worldwide, infects10–12 million people in Latin America. Differently from T. cruzi epimastigotes, trypomastigotes arecomplement-resistant and infective. CRPs, T-DAF, sialic acid and lipases explain at least part of this resis-tance. In vitro, T. cruzi calreticulin (TcCRT), a chaperone molecule that translocates from the ER to theparasite surface: (a) Inhibits the human classical complement activation, by interacting with C1, (b) Asa consequence, an increase in infectivity is evident and, (c) It inhibits angiogenesis and tumor growth.We report here that TcCRT also binds to the L-Ficolin collagenous portion, thus inhibiting approximatelybetween 35 and 64% of the human complement lectin pathway activation, initiated by L-Ficolin, a prop-erty not shared by H-Ficolin. While L-Ficolin binds to 60% of trypomastigotes and to 24% of epimastigotes,50% of the former and 4% of the latter display TcCRT on their surfaces. Altogether, these data indicatethat TcCRT is a parasite inhibitory receptor for Ficolins. The resulting evasive activities, together with theTcCRT capacity to inhibit C1, with a concomitant increase in infectivity, may represent T. cruzi strategiesto inhibit important arms of the innate immune response.