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Trypanosoma cruzi induces apoptosis in ex vivo infected human chorionic villi
J. Duaso a,1, G. Rojo a,1, F. Jaña c, N. Galanti b, G. Cabrera b, C. Bosco a, R. López-Muñoz c, J.D. Maya c, J. Ferreira c, U. Kemmerling a, d, *
Programa de Anatomía y Biologíadel Desarrollo, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile Programa de Biología Celular y Molecular, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile c Programa de Farmacología Molecular y Clínica, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile dDepartamento de Estomatología, Facultad de Ciencias de la Salud, Universidad de Talca, Talca, Chile
a r t i c l e i n f o
Article history: Accepted 23 February 2011 Keywords: Trypanosoma cruzi Apoptosis Human chorionic villi
a b s t r a c t
Chagas’ disease, produced by the haemoﬂagellated protozoan Trypanosoma cruzi (T. cruzi), is one of the most frequent endemic diseases in Latin America. Inspite that in the past few years T. cruzi congenital transmission has become of epidemiological importance, studies about this mechanism of infection are scarce. The placental tissue undergoes apoptosis throughout gestation, as part of its normal turnover. On the other hand, it is known that T. cruzi induces, delays or inhibits apoptosis in other mammalian tissues. In order to determine the effect ofparasite invasion on normal apoptosis in the placenta, explants of human chorionic villi were incubated with 105 trypomastigotes for 24 h. Effective infection was tested by visualizing T. cruzi antigens in histological preparations and by PCR. Upon infection, apoptotic cell death was determined by light and transmission electron microscopy, TUNEL analysis, measurement of caspase-3 like activityand immunohistochemical detection of caspase 3 cleaved cytokeratin 18. Our results clearly show that T. cruzi induces apoptosis in the chorionic villi and suggest that this is one of mechanisms used by the parasite to insure infection and invasion of human placenta and fetus. Ó 2011 Elsevier Ltd. All rights reserved.
1. Introduction American trypanosomiasis, or Chagas disease, is a zoonosiscaused by Trypanosoma cruzi, that is transmitted by haematophagous insects. Currently, 6e7 million people in the Americas from Mexico in the north to Argentina and Chile in the south are estimated to be infected . As a result of vector control (triatomids), the number of new cases per year has greatly decreased. Nonetheless, in the past few years congenital transmission of T. cruzi has increasinglybecome more important, and partly responsible for the globalization of Chagas’ disease , constituting a public health problem of increasing relevance . Congenital T. cruzi infection is associated with premature labor, low birth weight, and still births [1,4]. It has been suggested that the parasite reaches the fetus by crossing the placental barrier [4e6]. Nevertheless, knowledge of thecellular and molecular mechanisms of transplacental infection is scarce . It is thought that congenital
* Corresponding author. Programa de Anatomía y Biología del Desarrollo, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile. Tel.: þ56 2 9786261; fax: þ56 2 9786264. E-mail address: firstname.lastname@example.org (U. Kemmerling). 1 These authorscontributed equally to this work. 0143-4004/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.placenta.2011.02.005
Chagas’ disease is product of a complex interaction between the maternal immune response, placental factors, and the parasite [6,7]. The villous placenta plays an important role in preventing maternal pathogens from entering fetal circulation. It is a complex...