Exogenous calreticulin, incorporated onto non-infective Trypanosoma cruzi epimastigotes, promotes their internalization into mammal hosts cells

Chagas disease is an endemic pathology in Latin America, now emerging in developed countries, causedby the intracellular protozoan Trypanosoma cruzi, whose life cycle involves three stages: amastigotes,epimastigotes, and trypomastigotes. T. cruzi Calreticulin (TcCRT), an endoplasmic reticulum residentchaperone, translocates to the external cellular membrane, where it captures complement componentC1, ficolins and MBL, thus inactivating the classical and lectin pathways. Trypomastigote-bound C1 isdetected as an “eat me” signal by macrophages and promotes the infective process. Unlike infective try-pomastigotes, non-infective epimastigotes either do not express or express only marginal levels of TcCRTon their external membrane. We show that epimastigotes bind exogenous rTcCRT to their cellular mem-brane and, in the presence of C1q, this parasite form is internalized into normal fibroblasts. On the otherhand, Calreticulin (CRT)-deficient fibroblasts show impaired parasite internalization. In synthesis, CRTfrom both parasite and host cell origin is important in the establishment of C1q-dependent first contactsbetween parasites and host cells