Recently differentiated epimastigotes from Trypanosoma cruzi are infective to the mammalian host

• Published in: Molecular microbiology 2017-06, Vol.104 (5), p.712-736
• Main Authors: Kessler, Rafael Luis, Contreras, Víctor Tulio, Marliére, Newmar Pinto, Aparecida Guarneri, Alessandra, Villamizar Silva, Luz Helena, Mazzarotto, Giovanny Augusto Camacho Antevere, Batista, Michel, Soccol, Vanete Thomaz, Krieger, Marco Aurelio, Probst, Christian Macagnan
• Format: Article
• Language: English
• Subjects: Animals; Cell culture; Cell Differentiation - physiology; Chagas disease; Chagas Disease - parasitology; Complement; Complement system; Epimastigotes; Etiology; Host-Parasite Interactions; In vitro methods and tests; Infectivity; Insects; Life cycle engineering; Life Cycle Stages - physiology; Life cycles; Lysis; Mammals; Mice; Microbiology; Parasites; Proteins; Proteomics; Protozoa; Protozoan Proteins - metabolism; Replication; Trypanosoma cruzi - genetics; Trypanosoma cruzi - growth & development; Trypanosoma cruzi - metabolism; Trypanosoma cruzi - pathogenicity; Vector-borne diseases; Virulence
• ISSN: 0950-382X; 1365-2958
• DOI: 10.1111/mmi.13653

Summary Trypanosoma cruzi, the etiologic agent of Chagas disease, has a complex life cycle in which four distinct developmental forms alternate between the insect vector and the mammalian host. It is assumed that replicating epimastigotes present in the insect gut are not infective to mammalian host, a paradigm corroborated by the widely acknowledged fact that only this stage is susceptible to the complement system. In the present work, we establish a T. cruzi in vitro and in vivo epimastigogenesis model to analyze the biological aspects of recently differentiated epimastigotes (rdEpi). We show that both trypomastigote stages of T. cruzi (cell‐derived and metacyclic) are able to transform into epimastigotes (processes termed primary and secondary epimastigogenesis, respectively) and that rdEpi have striking properties in comparison to long‐term cultured epimastigotes: resistance to complement‐mediated lysis and both in vitro (cell culture) and in vivo (mouse) infectivity. Proteomics analysis of all T. cruzi stages reveled a cluster of proteins that were up‐regulated only in rdEpi (including ABC transporters and ERO1), suggesting a role for them in rdEpi virulence. The present work introduces a new experimental model for the study of host‐parasite interactions, showing that rdEpi can be infective to the mammalian host. Trypanosoma cruzi epimastigote stage (replicating form of insect vector) are considered non infective to the mammalian host, a centenary paradigm in Chagas disease research. Kessler et al challenges this hypothesis showing that recently differentiated epimastigotes (rdEpi) have distinct biological properties, being in vitro and in vivo infective, and expressing a distinct cluster of predicted surface proteins identified by shotgun proteomics. A new experimental model for the study of host‐parasite interactions in T. cruzi is introduced.