title: Mammalian cell invasion by closely related Trypanosoma species T. dionisii and T. cruzi.
abstract: Protozoan parasites of the genus Trypanosoma can infect virtually all mammalian species. Within this genus, Trypanosoma dionisii from bats and Trypanosoma cruzi that causes Chagas' disease, belonging to the subgenus Schizotrypanum, can invade mammalian cells. The mechanisms of cell invasion by T. dionisii are poorly understood. To address that question, metacyclic trypomastigotes (MT) and human epithelial HeLa cells were used. Similarly to genetically divergent T. cruzi strains G (TcI) and CL (TcVI), associated, respectively with marsupial and human infections, T. dionisii infectivity increased under nutritional stress, a condition that induces host cell lysosome exocytosis required for parasite internalization. For efficient internalization, T. dionisii depended on MT protein tyrosine kinase (PTK) and Ca(2+) mobilization from acidocalcisomes, whereas T. cruzi strains also relied on phosphatidylinositol 3-kinase (PI3K), protein kinase C (PKC) and Ca(2+) released from thapsigargin-sensitive compartments. T. dionisii-induced signaling in host cells implicated PKC and Ca(2+) mobilized from thapsigargin-sensitive stores, like T. cruzi, but without PI3K involvement. Unlike T. cruzi, T. dionisii metacyclic forms did not use l-proline as source of energy required for internalization. Molecules related to T. cruzi surface glycoproteins involved in MT-host cell interaction were undetectable in T. dionisii. The difference in the surface profile of the two species was also inferred from the susceptibility of T. dionisii metacyclic forms to complement-mediated lysis, as opposed to complete resistance of T. cruzi. In summary, the two Trypanosoma species display distinct surface profiles but invade host cells through a common mechanism involving lysosome mobilization to the site of parasite entry.
authors.affiliation: Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo, R. Pedro de Toledo, Brazil.
authors.forename: Fernando Yukio
authors.initials: FY
authors.lastname: Maeda
authors.forename: Cristian
authors.initials: C
authors.lastname: Cortez
authors.forename: Renan Melatto
authors.initials: RM
authors.lastname: Alves
authors.forename: Nobuko
authors.initials: N
authors.lastname: Yoshida
mesh_terms: D002118:Calcium / Q000378:metabolism; D004705:Endocytosis; D055354:Exosomes / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D014345:Trypanosoma / Q000472:pathogenicity*
chemical_list: D011494:Protein Kinases; D058539:Phosphatidylinositol 3-Kinase; D002118:Calcium