title: Different genotypes of Trypanosoma cruzi produce distinctive placental environment genetic response in chronic experimental infection.
abstract: Congenital infection of Trypanosoma cruzi allows transmission of this parasite through generations. Despite the problematic that this entails, little is known about the placenta environment genetic response produced against infection. We performed functional genomics by microarray analysis in C57Bl/6J mice comparing placentas from uninfected animals and from animals infected with two different T. cruzi strains: K98, a clone of the non-lethal myotropic CA-I strain (TcI), and VD (TcVI), isolated from a human case of congenital infection. Analysis of networks by GeneMANIA of differentially expressed genes showed that "Secretory Granule" was a pathway down-regulated in both infected groups, whereas "Innate Immune Response" and "Response to Interferon-gamma" were pathways up-regulated in VD infection but not in K98. Applying another approach, the GSEA algorithm that detects small changes in predetermined gene sets, we found that metabolic processes, transcription and macromolecular transport were down-regulated in infected placentas environment and some pathways related to cascade signaling had opposite regulation: over-represented in VD and down-regulated in K98 group. We also have found a stronger tropism to the placental organ by VD strain, by detection of parasite DNA and RNA, suggesting living parasites. Our study is the first one to describe in a murine model the genetic response of placental environment to T. cruzi infection and suggests the development of a strong immune response, parasite genotype-dependent, to the detriment of cellular metabolism, which may contribute to control infection preventing the risk of congenital transmission.
authors.affiliation: Grupo de Biología Molecular de la Enfermedad de Chagas (LaBMECh), Instituto de Investigaciones en Ingeniería Genética y Biología Molecular ''Dr. Héctor N. Torres" (INGEBI-CONICET), Buenos Aires, Argentina.
authors.forename: Natalia Anahí
authors.initials: NA
authors.lastname: Juiz
authors.affiliation: Departamento de Microbiología, Parasitología e Inmunología, Instituto de Investigaciones en Microbiología y Parasitología Médica (IMPaM), Facultad de Medicina, Universidad de Buenos Aires (UBA), Buenos Aires, Argentina.
authors.forename: María Elisa
authors.initials: ME
authors.lastname: Solana
authors.affiliation: Grupo de Biología Molecular de la Enfermedad de Chagas (LaBMECh), Instituto de Investigaciones en Ingeniería Genética y Biología Molecular ''Dr. Héctor N. Torres" (INGEBI-CONICET), Buenos Aires, Argentina.
authors.forename: Gonzalo Raúl
authors.initials: GR
authors.lastname: Acevedo
authors.affiliation: Grupo de Biología Molecular de la Enfermedad de Chagas (LaBMECh), Instituto de Investigaciones en Ingeniería Genética y Biología Molecular ''Dr. Héctor N. Torres" (INGEBI-CONICET), Buenos Aires, Argentina.
authors.forename: Alejandro Francisco
authors.initials: AF
authors.lastname: Benatar
authors.affiliation: Grupo de Biología Molecular de la Enfermedad de Chagas (LaBMECh), Instituto de Investigaciones en Ingeniería Genética y Biología Molecular ''Dr. Héctor N. Torres" (INGEBI-CONICET), Buenos Aires, Argentina.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Ramirez
authors.affiliation: Departamento de Bioquímica e Inmunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Priscilla Almeida
authors.initials: PA
authors.lastname: da Costa
authors.affiliation: Departamento de Bioquímica e Inmunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Andrea Mara
authors.initials: AM
authors.lastname: Macedo
authors.affiliation: Grupo de Biología Molecular de la Enfermedad de Chagas (LaBMECh), Instituto de Investigaciones en Ingeniería Genética y Biología Molecular ''Dr. Héctor N. Torres" (INGEBI-CONICET), Buenos Aires, Argentina.
authors.forename: Silvia Andrea
authors.initials: SA
authors.lastname: Longhi
authors.affiliation: Grupo de Biología Molecular de la Enfermedad de Chagas (LaBMECh), Instituto de Investigaciones en Ingeniería Genética y Biología Molecular ''Dr. Héctor N. Torres" (INGEBI-CONICET), Buenos Aires, Argentina.
authors.forename: Alejandro G
authors.identifier: 0000-0001-9805-3415
authors.initials: AG
authors.lastname: Schijman
mesh_terms: D000818:Animals; D014355:Chagas Disease / Q000469:parasitology* / Q000473:pathology; D002908:Chronic Disease; D004195:Disease Models, Animal; D005260:Female; D020869:Gene Expression Profiling; D005838:Genotype; D008810:Mice, Inbred C57BL; D046228:Microarray Analysis; D010920:Placenta / Q000469:parasitology* / Q000473:pathology*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000469:parasitology* / Q000473:pathology; D014349:Trypanosoma cruzi / Q000145:classification* / Q000235:genetics*