title: Phospholipase C gamma and ERK1/2 mitogen activated kinase pathways are differentially modulated by Trypanosoma cruzi during tissue invasion in human placenta.
abstract: Chagas' disease is caused by the haemophlagelated protozoan Trypanosoma cruzi (T. cruzi). During congenital transmission the parasite breaks down the placental barrier, however studies about the physiopathology of this process are scarce. Different signal transduction pathways are involved during cell invasion of the parasite. However, the possible role of those processes during tissue infection has not been studied. In the present study we analyzed the modulation of two signal transduction pathways, PLC-γ and ERK1/2 MAPK, during ex vivo infection of human placental chorionic villi explants. Chorionic villi from healthy woman placentas were incubated in the presence or absence of 10(5) or 10(6)T. cruzi trypomastigotes (DM28c strain) with or without specific inhibitors for each pathway. Effective infection was tested determining parasite DNA by PCR. The activation of PLC-γ and ERK1/2 MAPK signaling pathways was determined by western blotting and immunofluorescence. The low concentration of T. cruzi trypomastigotes activates both signaling pathways; however, the high concentration of parasite induces a modest activation of the PLC-γ pathway and impairs the ERK1/2 MAPK pathway activation. Interestingly, inhibition of any of those signaling pathways did not prevent parasite infection, as it was previously shown in cell cultures. We conclude that both signal transduction pathways are modulated during ex vivo T. cruzi infection of human placental chorionic villi explants.
authors.affiliation: Programa de Anatomía y Biología del Desarrollo, Instituto de Ciencias Biomédicas, Universidad de Chile, Chile.
authors.forename: Christian
authors.initials: C
authors.lastname: Castillo
authors.forename: Arturo
authors.initials: A
authors.lastname: Villarroel
authors.forename: Juan
authors.initials: J
authors.lastname: Duaso
authors.forename: Norbel
authors.initials: N
authors.lastname: Galanti
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Cabrera
authors.forename: Juan Diego
authors.initials: JD
authors.lastname: Maya
authors.forename: Ulrike
authors.initials: U
authors.lastname: Kemmerling
mesh_terms: D000818:Animals; D002522:Chlorocebus aethiops; D002824:Chorionic Villi / Q000201:enzymology / Q000469:parasitology; D005260:Female; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology*; D051966:Phospholipase C gamma / Q000378:metabolism*; D010920:Placenta / Q000201:enzymology* / Q000469:parasitology*; D011247:Pregnancy; D015398:Signal Transduction / Q000502:physiology; D014709:Vero Cells
chemical_list: D051966:Phospholipase C gamma