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

• Trypanosoma cruzi (T. cruzi) calreticulin (TcCRT) binds to the L-Ficolin.
• TcCRT/L-Ficolin binding inhibits 35–64% the complement lectin pathway activation.
• While L-Ficolin binds to 60% of trypomastigotes and to 24% of epimastigotes.
• Trypomastigotes (50%) and epimastigotes (4%) display TcCRT on their surfaces.
• Our data indicate that TcCRT is a parasite inhibitory receptor for Ficolins.
• L-Ficolin/TcCRT binding could be a T. cruzi strategy to inhibit the complement.

Trypanosoma cruzi, the agent of Chagas’ disease, the sixth neglected tropical disease worldwide, infects 10–12 million people in Latin America. Differently from T. cruzi epimastigotes, trypomastigotes are complement-resistant and infective. CRPs, T-DAF, sialic acid and lipases explain at least part of this resistance. In vitro, T. cruzi calreticulin (TcCRT), a chaperone molecule that translocates from the ER to the parasite surface: (a) Inhibits the human classical complement activation, by interacting with C1, (b) As a 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 approximately between 35 and 64% of the human complement lectin pathway activation, initiated by L-Ficolin, a property 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 indicate that TcCRT is a parasite inhibitory receptor for Ficolins. The resulting evasive activities, together with the TcCRT capacity to inhibit C1, with a concomitant increase in infectivity, may represent T. cruzi strategies to inhibit important arms of the innate immune response.