title: Exogenous Calreticulin, incorporated onto non-infective Trypanosoma cruzi epimastigotes, promotes their internalization into mammal host cells.
abstract: Chagas disease is an endemic pathology in Latin America, now emerging in developed countries, caused by the intracellular protozoan Trypanosoma cruzi, whose life cycle involves three stages: amastigotes, epimastigotes, and trypomastigotes. T. cruzi Calreticulin (TcCRT), an endoplasmic reticulum resident chaperone, translocates to the external cellular membrane, where it captures complement component C1, ficolins and MBL, thus inactivating the classical and lectin pathways. Trypomastigote-bound C1 is detected as an "eat me" signal by macrophages and promotes the infective process. Unlike infective trypomastigotes, non-infective epimastigotes either do not express or express only marginal levels of TcCRT on their external membrane. We show that epimastigotes bind exogenous rTcCRT to their cellular membrane and, in the presence of C1q, this parasite form is internalized into normal fibroblasts. On the other hand, Calreticulin (CRT)-deficient fibroblasts show impaired parasite internalization. In synthesis, CRT from both parasite and host cell origin is important in the establishment of C1q-dependent first contacts between parasites and host cells.
authors.affiliation: Laboratory of Immunology of the Microbial Aggression, Immunology Program, ICBM, Faculty of Medicine, University of Chile, Santiago, Chile.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Sosoniuk-Roche
authors.affiliation: Laboratory of Immunology of the Microbial Aggression, Immunology Program, ICBM, Faculty of Medicine, University of Chile, Santiago, Chile.
authors.forename: Gerardo
authors.initials: G
authors.lastname: Vallejos
authors.affiliation: Laboratory of Immunology of the Microbial Aggression, Immunology Program, ICBM, Faculty of Medicine, University of Chile, Santiago, Chile.
authors.forename: Lorena
authors.initials: L
authors.lastname: Aguilar-Guzmán
authors.affiliation: Laboratory of Immunology of the Microbial Aggression, Immunology Program, ICBM, Faculty of Medicine, University of Chile, Santiago, Chile.
authors.forename: Javier
authors.initials: J
authors.lastname: Pizarro-Bäuerle
authors.affiliation: Laboratory of Immunology of the Microbial Aggression, Immunology Program, ICBM, Faculty of Medicine, University of Chile, Santiago, Chile.
authors.forename: Katherine
authors.initials: K
authors.lastname: Weinberger
authors.affiliation: Laboratory of Immunology of the Microbial Aggression, Immunology Program, ICBM, Faculty of Medicine, University of Chile, Santiago, Chile.
authors.forename: Carlos
authors.initials: C
authors.lastname: Rosas
authors.affiliation: Laboratory of Immunology of the Microbial Aggression, Immunology Program, ICBM, Faculty of Medicine, University of Chile, Santiago, Chile. Electronic address: cevalck@u.uchile.cl.
authors.forename: Carolina
authors.initials: C
authors.lastname: Valck
authors.affiliation: Department of Biochemistry, University of Alberta, Alberta, Canada.
authors.forename: Marek
authors.initials: M
authors.lastname: Michalak
authors.affiliation: Laboratory of Immunology of the Microbial Aggression, Immunology Program, ICBM, Faculty of Medicine, University of Chile, Santiago, Chile. Electronic address: aferreir@med.uchile.cl.
authors.forename: Arturo
authors.initials: A
authors.lastname: Ferreira
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D037282:Calreticulin / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D014355:Chagas Disease / Q000276:immunology / Q000469:parasitology; D015922:Complement C1q / Q000276:immunology / Q000378:metabolism; D004705:Endocytosis / Q000276:immunology*; D005347:Fibroblasts / Q000378:metabolism / Q000469:parasitology; D055786:Gene Knockout Techniques; D006790:Host-Parasite Interactions / Q000276:immunology*; D051379:Mice; D011485:Protein Binding; D014349:Trypanosoma cruzi / Q000276:immunology* / Q000378:metabolism / Q000472:pathogenicity; D037521:Virulence Factors / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D037282:Calreticulin; D037521:Virulence Factors; D015922:Complement C1q
keywords: Calreticulin; Chagas; Complement; Infection; Trypanosoma cruzi