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Trypanosoma cruzi and Toxoplasma gondii are two zoonotic parasites that constitute significant human and animal health threats, causing a significant economic burden worldwide. Both parasites can be transmitted congenitally, but transmission rates for T. gondii are high, contrary to what has been observed for T. cruzi. The probability of congenital transmission depends on complex interactions between the pathogen and the host, including the modulation of host cell gene expression by miRNAs. During ex vivo infection of canine and ovine placental explants, we evaluated the expression of 3 miRNAs (miR-30e-3p, miR-3074-5p, and miR-127-3p) previously associated with parasitic and placental diseases and modulated by both parasites. In addition, we identified the possible target genes of the miRNAs by using computational prediction tools and performed GO and KEGG enrichment analyses to identify the biological functions and associated pathologies. The three miRNAs are differentially expressed in the canine and ovine placenta in response to T. cruzi and T. gondii. We conclude that the observed differential expression and associated functions might explain, at least partially, the differences in transmission rates and susceptibility to parasite infection in different species.

Trypanosoma cruzi, the causative agent of Chagas disease, and Toxoplasma gondii, which is responsible for Toxoplasmosis, are two parasites that cause significant protozoan zoonoses and consequently important economic losses in human, companion animals and livestock. For the congenital transmission to occur, both parasites must cross the barrier present in the mammalian placenta, which differs between species. Particularly, hemochorial, endotheliochorial and epitheliochorial placental barriers are present, respectively, in human, dog and sheep. The type of placental barrier has been associated with the probability of transmission of pathogens. In this study, we used experimental placental ex vivo infection models of T. cruzi and T. gondii in the above-mentioned mammals in order to study tissue alterations and to compare infection efficiency. Here, we infected placental term explants from human, dog and sheep and analyzed tissue damage by standard histological and histochemical methods. Comparative infection efficiency was determined by quantitative PCR. Both parasites are able to infect the different placental explants; however, more T. gondii parasites were detected, and T. gondii causes a more severe tissue damage in human and canine explants than T. cruzi. The histopathological changes observed in ovine placenta explants were similar in presence of both parasites. We conclude that the infection efficiency of T. gondii is higher, compared to T. cruzi, during the ex vivo infection of human, canine and ovine placental explants. In addition, the ex vivo infection of mammalian placental explants constitutes an interesting experimental approach to study part of the infection mechanisms as well as host responses during congenital infection of both parasites.

Congenital Chagas disease, caused by Trypanosoma cruzi (T. cruzi), is partially responsible for the increasing globalization of Chagas disease despite its low transmission. During congenital transmission, the parasite reaches the fetus by crossing the placental barrier. However, the success or impairment of congenital transmission of the parasite is the product of a complex interaction between the parasite, the maternal and fetus/newborn immune responses and placental factors. There is other evidence apart from the low congenital transmission rates, which suggests the presence of defense mechanisms against T. cruzi. Thus, the typical amastigote nests (intracellular parasites) cannot be observed in placentas from mothers with chronic Chagas disease nor in human placental chorionic villi explants infected in vitro with the parasite. In the latter, only a few parasite antigens and DNA are identified. Accordingly, other infections of the placenta are not commonly observed. All these evidences suggest that the placenta can mount defense mechanisms against T. cruzi.

Background 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. On the other hand, the placenta is considered an immune regulatory organ since it acts as a modulator of fetal and maternal immune responses. We have previously proposed that local placental factors, such as the epithelial turnover of the trophoblast and the innate immune response initiated by Toll-like receptors (TLRs), might prevent parasite infection and congenital transmission. Here, we studied in an ex vivo infected human placental chorionic villi explant HPCVE model, the relationship between TLR-2 activation in response to T. cruzi trypomastigotes, the secreted profile of cytokines, the integrity of the placental barrier and the expression of trophoblast turnover markers. Results TLR-2 inhibition increases the parasite induced histopathological damage, prevents secretion of IL-6 and IL-10, decreases expression of PCNA (proliferation marker) and of β-hCG (differentiation marker) while increasing caspase 3 activity (cell death marker). Conclusion Our results suggest that TLR-2 is not only involved in the local secretion of cytokines but also regulates, at least partially, the trophoblast turnover.

Chagas disease and toxoplasmosis, caused by Trypanosoma cruzi and Toxoplasma gondii, respectively, are important zoonotic diseases affecting humans, companion animals, and livestock, responsible for major health and economic burden. Both parasites can be transmitted vertically in different mammalian species through the placenta. Of note, the transmission rate of T. cruzi is low in dogs, whereas that of T. gondii is high in sheep. The probability of congenital infection depends on complex parasite-host interactions; parasite factors, maternal and fetal immune responses and placental responses all have a role in infection establishment. Since the innate immune response is regulated, at least partially, by NF-κB signaling pathways, our main objective was to determine the effect of ex vivo infection of canine (CPE) and ovine (OPE) placental explants with both parasites, on the activation of canonical and non-canonical NF-κB pathways and its relation to infection. Here, we show that T. cruzi activates both the NF-κB canonical and non-canonical pathways in CPE and OPE, unlike T. gondii, that activates only the canonical pathway in CPE and has no effect on the non-canonical pathway in both explants. Moreover, the inhibition of either or both NF-κB pathways increases the DNA load of T. cruzi in both explants, modulates, on the other hand, T. gondii infection in a differential fashion. Overall, we conclude that the differential modulation of the NF-κB pathways by both pathogens in placental explants might explain, at least partially, the differences in transmission rates of T. cruzi and T. gondii in different mammalian species.

Chagas disease and toxoplasmosis, caused by Trypanosoma cruzi and Toxoplasma gondii, respectively, are important zoonotic diseases affecting humans, companion animals, and livestock, responsible for major health and economic burden. Both parasites can be transmitted vertically in different mammalian species through the placenta. Of note, the transmission rate of T. cruzi is low in dogs, whereas that of T. gondii is high in sheep. The probability of congenital infection depends on complex parasite-host interactions; parasite factors, maternal and fetal immune responses and placental responses all have a role in infection establishment. Since the innate immune response is regulated, at least partially, by NF-κB signaling pathways, our main objective was to determine the effect of ex vivo infection of canine (CPE) and ovine (OPE) placental explants with both parasites, on the activation of canonical and non-canonical NF-κB pathways and its relation to infection. Here, we show that T. cruzi activates both the NF-κB canonical and non-canonical pathways in CPE and OPE, unlike T. gondii, that activates only the canonical pathway in CPE and has no effect on the non-canonical pathway in both explants. Moreover, the inhibition of either or both NF-κB pathways increases the DNA load of T. cruzi in both explants, modulates, on the other hand, T. gondii infection in a differential fashion. Overall, we conclude that the differential modulation of the NF-κB pathways by both pathogens in placental explants might explain, at least partially, the differences in transmission rates of T. cruzi and T. gondii in different mammalian species.

Congenital Chagas disease, caused by Trypanosoma cruzi (T. cruzi), has become epidemiologically relevant. The probability of congenital transmission depends on the maternal and developing fetal/newborn immune responses, placental factors and importantly, the virulence of the parasite. It has been proposed, that different genotypes of T. cruzi and their associated pathogenicity, virulence and tissue tropism may play an important role in congenital infection. Since there is no laboratory or animal model that recapitulates the complexities of vertical transmission in humans, here we studied parasite infectivity in human placental explants (HPE) as well as in the human trophoblast-derived cell line BeWo of the Y(DTU II) and the VD (TcVI) T. cruzi strains; the latter was isolated from a human case of congenital infection. Our results show that the VD strain is more infective and pathogenic than the Y strain, as demonstrated by qPCR and cell counting as well as by histopathological analysis. The present study constitutes the first approach to study the relationship between parasite two parasite strains from different genotypes and the infection efficiency in human placenta. Fil: Medina, Lisvaneth. Universidad de Chile; Chile Fil: Castillo, Christian. Universidad de Chile; Chile Fil: Liempi, Ana. Universidad de Chile; Chile Fil: Herbach, Mathias. Universidad de Chile; Chile Fil: Cabrera, Gonzalo. Universidad de Chile; Chile Fil: Valenzuela, Lucía. Universidad de Chile; Chile Fil: Galanti, Norbel. Universidad de Chile; Chile Fil: Curto, Maria de Los Angeles. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina Fil: Schijman, Alejandro Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina Fil: Kemmerling, Ulrike. Universidad de Chile; Chile