Ex vivo infection of human placental explants with Trypanosoma cruzi and Toxoplasma gondii: Differential activation of NF kappa B signaling pathways

Liempi, Ana; Castillo, Christian; Medina, Lisvaneth; Rojas, Maura; Maya, Juan Diego; Parraguez, Vı́ctor H.; Kemmerling, Ulrike

doi:10.1016/j.actatropica.2019.105153

Cited by 12 publications

(14 citation statements)

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“…Our results showed that in HPEs, T. gondii and T. cruzi infection increased miR-146a expression. Our previous studies showed that both parasites modulate placental immune response differentially through TLRs and NFkB pathways in HPEs (9, 10) Interestingly, the inhibition of these pathways increased the DNA loads of both parasites in HPEs (10). Increased T. gondii infection in placental tissue is also induced by TLR-4 inhibition (9).…”

Section: Discussionmentioning

confidence: 99%

“…Expression of miR-210 can be directly regulated by the specific binding of NF-κB p50 to its putative promoter ( 53 ). In this context, it is important to mention that T. cruzi , but not T. gondii , infection of HPE activates both NF-κB signaling pathways ( 10 ). Therefore, the increased level of miR-210 might be a placental response to signal transduction pathway activation.…”

Section: Discussionmentioning

confidence: 99%

“…Three independent experiments were carried out in triplicates; HPEs from each placenta were infected with either T. cruzi or T. gondii parasites. The parasite load in the HPEs was confirmed by real-time PCR as described previously by us ( 9 , 10 , 26 ).…”

Section: Methodsmentioning

confidence: 99%

“…T. cruzi has a low transmission rate (1–12%) ( 6 , 8 ) while T. gondii has a high transmission rate (22–72%) ( 3 ). Moreover, both parasites elicit a different local placental immune response that might be related to infection susceptibility ( 9 , 10 ). Thus, T. cruzi and T. gondi infection is related to the expression and activation of different Toll-like receptors, which in turn mediate the secretion of different cytokines and chemokines in defense against both parasites in the placenta ( 9 , 11 ).…”

Section: Introductionmentioning

confidence: 99%

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Trypanosoma cruzi and Toxoplasma gondii Induce a Differential MicroRNA Profile in Human Placental Explants

et al. 2020

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Trypanosoma cruzi and Toxoplasma gondii are two parasites than can be transmitted from mother to child through the placenta. However, congenital transmission rates are low for T. cruzi and high for T. gondii. Infection success or failure depends on complex parasite-host interactions in which parasites can alter host gene expression by modulating non-coding RNAs such as miRNAs. As of yet, there are no reports on altered miRNA expression in placental tissue in response to either parasite. Therefore, we infected human placental explants ex vivo by cultivation with either T. cruzi or T. gondii for 2 h. We then analyzed the miRNA expression profiles of both types of infected tissue by miRNA sequencing and quantitative PCR, sequence-based miRNA target prediction, pathway functional enrichment, and upstream regulator analysis of differentially expressed genes targeted by differentially expressed miRNAs. Both parasites induced specific miRNA profiles. GO analysis revealed that the in silico predicted targets of the differentially expressed miRNAs regulated different cellular processes involved in development and immunity, and most of the identified KEGG pathways were related to chronic diseases and infection. Considering that the differentially expressed miRNAs identified here modulated crucial host cellular targets that participate in determining the success of infection, these miRNAs might explain the differing congenital transmission rates between the two parasites. Molecules of the different pathways that are regulated by miRNAs and modulated during infection, as well as the miRNAs themselves, may be potential targets for the therapeutic control of either congenital Chagas disease or toxoplasmosis.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Trypanosoma cruzi and Toxoplasma gondii Induce a Differential MicroRNA Profile in Human Placental Explants

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“…That is the case of the kinetoplastid Trypanosoma cruzi (T. cruzi), where only a few parasite antigens and DNA can be identified in human chorionic villi (Duaso et al, 2010). Additionally, the presence of T. cruzi activates local placental defense mechanisms such as the epithelial turnover of the BLT and secretion of pro-inflammatory cytokines through Toll-like receptors (TLR) activation and NFkB signaling (Liempi et al, 2016(Liempi et al, , 2019Castillo et al, 2017a,b).…”

Section: Host-apicomplexan Interactions At the Mammalian Placentamentioning

confidence: 99%

Congenital Transmission of Apicomplexan Parasites: A Review

et al. 2021

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Apicomplexans are a group of pathogenic protists that cause various diseases in humans and animals that cause economic losses worldwide. These unicellular eukaryotes are characterized by having a complex life cycle and the ability to evade the immune system of their host organism. Infections caused by some of these parasites affect millions of pregnant women worldwide, leading to various adverse maternal and fetal/placental effects. Unfortunately, the exact pathogenesis of congenital apicomplexan diseases is far from being understood, including the mechanisms of how they cross the placental barrier. In this review, we highlight important aspects of the diseases caused by species of Plasmodium, Babesia, Toxoplasma, and Neospora, their infection during pregnancy, emphasizing the possible role played by the placenta in the host-pathogen interaction.

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Ex vivo infection of canine and ovine placental explants with Trypanosoma cruzi and Toxoplasma gondii: differential activation of NF kappa B signaling pathways

et al. 2021

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Ex vivo infection of human placental explants with Trypanosoma cruzi and Toxoplasma gondii: Differential activation of NF kappa B signaling pathways

Cited by 12 publications

References 51 publications

Trypanosoma cruzi and Toxoplasma gondii Induce a Differential MicroRNA Profile in Human Placental Explants

Trypanosoma cruzi and Toxoplasma gondii Induce a Differential MicroRNA Profile in Human Placental Explants

Congenital Transmission of Apicomplexan Parasites: A Review

Ex vivo infection of canine and ovine placental explants with Trypanosoma cruzi and Toxoplasma gondii: differential activation of NF kappa B signaling pathways

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