title: Caspase-8 activity is part of the BeWo trophoblast cell defense mechanisms against Trypanosoma cruzi infection.
abstract: Congenital Chagas disease is caused by the protozoan parasite Trypanosoma cruzi that must cross the placental barrier during transmission. The trophoblast constitutes the first tissue in contact with the maternal-blood circulating parasite. Importantly, the congenital transmission rates are low, suggesting the presence of local placental defense mechanisms. Cellular proliferation and differentiation as well as apoptotic cell death are induced by the parasite and constitute part of the epithelial turnover of the trophoblast, which has been suggested to be part of those placental defenses. On the other hand, caspase-8 is an essential molecule in the modulation of trophoblast turnover by apoptosis and by epithelial differentiation. As an approach to study whether T. cruzi induced trophoblast turnover and infection is mediated by caspase-8, we infected BeWo cells (a trophoblastic cell line) with the parasite and determined in the infected cells the expression and enzymatic activity of caspase-8, DNA synthesis (as proliferation marker), β-human chorionic gonadotropin (β-hCG) (as differentiation marker) and activity of Caspase-3 (as apoptotic death marker). Parasite load in BeWo cells was measured by DNA quantification using qPCR and cell counting. Our results show that T. cruzi induces caspase-8 activity and that its inhibition increases trophoblast cells infection while decreases parasite induced cellular differentiation and apoptotic cell death, but not cellular proliferation. Thus, caspase-8 activity is part of the BeWo trophoblast cell defense mechanisms against T. cruzi infection. Together with our previous results, we suggest that the trophoblast turnover is part of local placental anti-parasite mechanisms.
authors.affiliation: Programa de Anatomía y Biología del Desarrollo, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Chile.
authors.forename: Ileana
authors.initials: I
authors.lastname: Carrillo
authors.affiliation: Programa de Anatomía y Biología del Desarrollo, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Chile; Departamento de Estomatología, Facultad de Ciencias de la Salud, Universidad de Talca, Chile.
authors.forename: Daniel
authors.initials: D
authors.lastname: Droguett
authors.affiliation: Programa de Anatomía y Biología del Desarrollo, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Chile.
authors.forename: Christian
authors.initials: C
authors.lastname: Castillo
authors.affiliation: Programa de Anatomía y Biología del Desarrollo, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Chile.
authors.forename: Ana
authors.initials: A
authors.lastname: Liempi
authors.affiliation: Programa de Anatomía y Biología del Desarrollo, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Chile.
authors.forename: Lorena
authors.initials: L
authors.lastname: Muñoz
authors.affiliation: Programa de Farmacología Molecular y Clínica, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Chile.
authors.forename: Juan Diego
authors.initials: JD
authors.lastname: Maya
authors.affiliation: Programa de Biología Celular y Molecular, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Chile.
authors.forename: Norbel
authors.initials: N
authors.lastname: Galanti
authors.affiliation: Programa de Anatomía y Biología del Desarrollo, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Chile. Electronic address: ukemmerling@med.uchile.cl.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Kemmerling
mesh_terms: D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000276:immunology / Q000378:metabolism*; D061945:Caspase Inhibitors / Q000494:pharmacology; D002460:Cell Line; D002522:Chlorocebus aethiops; D005260:Female; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism; D006801:Humans; D014327:Trophoblasts / Q000201:enzymology* / Q000276:immunology / Q000469:parasitology*; D014349:Trypanosoma cruzi / Q000276:immunology*; D014709:Vero Cells
chemical_list: D061945:Caspase Inhibitors; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D053148:Caspase 3; D053181:Caspase 8
keywords: Caspase-8; Congenital Chagas disease; Trophoblast defense mechanism