Role of placental barrier integrity in infection by Trypanosoma cruzi.
American trypanosomiasis has long been a neglected disease endemic in LatinAmerica, but congenital transmission has now spread Chagas disease to cause a global health problem. As the early stages of the infection of placental tissue and the vertical transmission by Trypanosoma cruzi are still not well understood, it is important to investigate the relevance of the first structure of the placental barrier in chorionic villi infection by T. cruzi during the initial stage of the infection. Explants of human chorionic villi from healthy pregnant women at term were denuded of their syncytiotrophoblast and co-cultured for 3h, 24h and 96h with 800,000 trypomastigotes (simulating acute infection). T. cruzi infected cells were identified by immunohistochemistry for cytokeratin-7 (+cytotrophoblast) and CD68 (+macrophages), and the infection was quantified. In placental tissue, the parasite load was analyzed by qPCR and microscopy, and the motile trypomastigotes were quantified in culture supernatant. In denuded chorionic villous, the total area occupied by the parasite (451.23μm2, 1.33%) and parasite load (RQ: 87) was significantly higher (p<0.05) than in the entire villous (control) (5.98μm2, 0.016%) (RQ:1) and with smaller concentration of nitric oxide. Stromal non-macrophage cells were infected as well as cytotrophoblasts and some macrophages, but with significant differences being observed. The parasite quantity in the culture supernatant was significantly higher (p<0.05) in denuded culture explants from 96h of culture. Although the human complete chorionic villi limited the infection, the detachment of the first structure of the placenta barrier (syncytiotrophoblast) increased both the infection of the villous stroma and the living trypomastigotes in the culture supernatant. Therefore structural and functional alterations to chorionic villi placental barrier reduce placental defenses and may contribute to the vertical transmission of Chagas.
Cell Biology, Histology and Embryology Department, Facultad Cs. Médicas. Instituto de Biología Celular, Universidad Nacional de Córdoba-INICSA (CONICET), Argentina; Histology and Cytology, Medicine, Universidad Nacional de Villa María, Córdoba, Argentina. Electronic address: cintiadiaz@yahoo.com.
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Díaz-Luján
Cell Biology, Histology and Embryology Department, Facultad Cs. Médicas. Instituto de Biología Celular, Universidad Nacional de Córdoba-INICSA (CONICET), Argentina.
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Triquell
Programa de Anatomía del Desarrollo, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Chile.
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Castillo
Hospital La Paz, Universidad Autónoma de Madrid, Spain.
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Hardisson
Programa de Anatomía del Desarrollo, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Chile.
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Kemmerling
Cell Biology, Histology and Embryology Department, Facultad Cs. Médicas. Instituto de Biología Celular, Universidad Nacional de Córdoba-INICSA (CONICET), Argentina; Histology, Embryology and Genetic-IICSHUM, Health Department, Universidad Nacional de La Rioja, Argentina; Histology and Cytology, Medicine, Universidad Nacional de Villa María, Córdoba, Argentina. Electronic address: rfretes@cmefcm.uncor.edu.
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Fretes
D015703:Antigens, CD / Q000276:immunology; D015214:Antigens, Differentiation, Myelomonocytic / Q000276:immunology; D014355:Chagas Disease / Q000635:transmission*; D002824:Chorionic Villi / Q000469:parasitology*; D018920:Coculture Techniques; D005260:Female; D006801:Humans; D018445:Infectious Disease Transmission, Vertical; D053552:Keratin-7 / Q000276:immunology; D009569:Nitric Oxide; D010920:Placenta / Q000469:parasitology; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D014349:Trypanosoma cruzi / Q000378:metabolism*; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D053552:Keratin-7; D009569:Nitric Oxide; C067980:CD68 antigen, human; D000097382:CD68 Molecule
Congenital Chagas disease; Human placenta; Placental barrier; Syncytiotrophoblast; Trypanosoma cruzi