Cargando…

Ex Vivo Infection of Human Placental Explants by Trypanosoma cruzi Reveals a microRNA Profile Similar to That Seen in Trophoblast Differentiation

Congenital Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, is responsible for 22.5% of new cases each year. However, placental transmission occurs in only 5% of infected mothers and it has been proposed that the epithelial turnover of the trophoblast can be considered a local pla...

Descripción completa

Detalles Bibliográficos
Autores principales: Medina, Lisvaneth, Guerrero-Muñoz, Jesús Alejandro, Liempi, Ana Isabel, Castillo, Christian, Ortega, Yessica, Sepúlveda, Alfredo, Salomó, Fernando, Maya, Juan Diego, Kemmerling, Ulrike
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8952303/
https://www.ncbi.nlm.nih.gov/pubmed/35335686
http://dx.doi.org/10.3390/pathogens11030361
_version_ 1784675581667835904
author Medina, Lisvaneth
Guerrero-Muñoz, Jesús Alejandro
Liempi, Ana Isabel
Castillo, Christian
Ortega, Yessica
Sepúlveda, Alfredo
Salomó, Fernando
Maya, Juan Diego
Kemmerling, Ulrike
author_facet Medina, Lisvaneth
Guerrero-Muñoz, Jesús Alejandro
Liempi, Ana Isabel
Castillo, Christian
Ortega, Yessica
Sepúlveda, Alfredo
Salomó, Fernando
Maya, Juan Diego
Kemmerling, Ulrike
author_sort Medina, Lisvaneth
collection PubMed
description Congenital Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, is responsible for 22.5% of new cases each year. However, placental transmission occurs in only 5% of infected mothers and it has been proposed that the epithelial turnover of the trophoblast can be considered a local placental defense against the parasite. Thus, Trypanosoma cruzi induces cellular proliferation, differentiation, and apoptotic cell death in the trophoblast, which are regulated, among other mechanisms, by small non-coding RNAs such as microRNAs. On the other hand, ex vivo infection of human placental explants induces a specific microRNA profile that includes microRNAs related to trophoblast differentiation such as miR-512-3p miR-515-5p, codified at the chromosome 19 microRNA cluster. Here we determined the expression validated target genes of miR-512-3p and miR-515-5p, specifically human glial cells missing 1 transcription factor and cellular FLICE-like inhibitory protein, as well as the expression of the main trophoblast differentiation marker human chorionic gonadotrophin during ex vivo infection of human placental explants, and examined how the inhibition or overexpression of both microRNAs affects parasite infection. We conclude that Trypanosoma cruzi-induced trophoblast epithelial turnover, particularly trophoblast differentiation, is at least partially mediated by placenta-specific miR-512-3p and miR-515-5p and that both miRNAs mediate placental susceptibility to ex vivo infection of human placental explants. Knowledge about the role of parasite-modulated microRNAs in the placenta might enable their use as biomarkers, as prognostic and therapeutic tools for congenital Chagas disease in the future.
format Online
Article
Text
id pubmed-8952303
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-89523032022-03-26 Ex Vivo Infection of Human Placental Explants by Trypanosoma cruzi Reveals a microRNA Profile Similar to That Seen in Trophoblast Differentiation Medina, Lisvaneth Guerrero-Muñoz, Jesús Alejandro Liempi, Ana Isabel Castillo, Christian Ortega, Yessica Sepúlveda, Alfredo Salomó, Fernando Maya, Juan Diego Kemmerling, Ulrike Pathogens Article Congenital Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, is responsible for 22.5% of new cases each year. However, placental transmission occurs in only 5% of infected mothers and it has been proposed that the epithelial turnover of the trophoblast can be considered a local placental defense against the parasite. Thus, Trypanosoma cruzi induces cellular proliferation, differentiation, and apoptotic cell death in the trophoblast, which are regulated, among other mechanisms, by small non-coding RNAs such as microRNAs. On the other hand, ex vivo infection of human placental explants induces a specific microRNA profile that includes microRNAs related to trophoblast differentiation such as miR-512-3p miR-515-5p, codified at the chromosome 19 microRNA cluster. Here we determined the expression validated target genes of miR-512-3p and miR-515-5p, specifically human glial cells missing 1 transcription factor and cellular FLICE-like inhibitory protein, as well as the expression of the main trophoblast differentiation marker human chorionic gonadotrophin during ex vivo infection of human placental explants, and examined how the inhibition or overexpression of both microRNAs affects parasite infection. We conclude that Trypanosoma cruzi-induced trophoblast epithelial turnover, particularly trophoblast differentiation, is at least partially mediated by placenta-specific miR-512-3p and miR-515-5p and that both miRNAs mediate placental susceptibility to ex vivo infection of human placental explants. Knowledge about the role of parasite-modulated microRNAs in the placenta might enable their use as biomarkers, as prognostic and therapeutic tools for congenital Chagas disease in the future. MDPI 2022-03-16 /pmc/articles/PMC8952303/ /pubmed/35335686 http://dx.doi.org/10.3390/pathogens11030361 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Medina, Lisvaneth
Guerrero-Muñoz, Jesús Alejandro
Liempi, Ana Isabel
Castillo, Christian
Ortega, Yessica
Sepúlveda, Alfredo
Salomó, Fernando
Maya, Juan Diego
Kemmerling, Ulrike
Ex Vivo Infection of Human Placental Explants by Trypanosoma cruzi Reveals a microRNA Profile Similar to That Seen in Trophoblast Differentiation
title Ex Vivo Infection of Human Placental Explants by Trypanosoma cruzi Reveals a microRNA Profile Similar to That Seen in Trophoblast Differentiation
title_full Ex Vivo Infection of Human Placental Explants by Trypanosoma cruzi Reveals a microRNA Profile Similar to That Seen in Trophoblast Differentiation
title_fullStr Ex Vivo Infection of Human Placental Explants by Trypanosoma cruzi Reveals a microRNA Profile Similar to That Seen in Trophoblast Differentiation
title_full_unstemmed Ex Vivo Infection of Human Placental Explants by Trypanosoma cruzi Reveals a microRNA Profile Similar to That Seen in Trophoblast Differentiation
title_short Ex Vivo Infection of Human Placental Explants by Trypanosoma cruzi Reveals a microRNA Profile Similar to That Seen in Trophoblast Differentiation
title_sort ex vivo infection of human placental explants by trypanosoma cruzi reveals a microrna profile similar to that seen in trophoblast differentiation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8952303/
https://www.ncbi.nlm.nih.gov/pubmed/35335686
http://dx.doi.org/10.3390/pathogens11030361
work_keys_str_mv AT medinalisvaneth exvivoinfectionofhumanplacentalexplantsbytrypanosomacruzirevealsamicrornaprofilesimilartothatseenintrophoblastdifferentiation
AT guerreromunozjesusalejandro exvivoinfectionofhumanplacentalexplantsbytrypanosomacruzirevealsamicrornaprofilesimilartothatseenintrophoblastdifferentiation
AT liempianaisabel exvivoinfectionofhumanplacentalexplantsbytrypanosomacruzirevealsamicrornaprofilesimilartothatseenintrophoblastdifferentiation
AT castillochristian exvivoinfectionofhumanplacentalexplantsbytrypanosomacruzirevealsamicrornaprofilesimilartothatseenintrophoblastdifferentiation
AT ortegayessica exvivoinfectionofhumanplacentalexplantsbytrypanosomacruzirevealsamicrornaprofilesimilartothatseenintrophoblastdifferentiation
AT sepulvedaalfredo exvivoinfectionofhumanplacentalexplantsbytrypanosomacruzirevealsamicrornaprofilesimilartothatseenintrophoblastdifferentiation
AT salomofernando exvivoinfectionofhumanplacentalexplantsbytrypanosomacruzirevealsamicrornaprofilesimilartothatseenintrophoblastdifferentiation
AT mayajuandiego exvivoinfectionofhumanplacentalexplantsbytrypanosomacruzirevealsamicrornaprofilesimilartothatseenintrophoblastdifferentiation
AT kemmerlingulrike exvivoinfectionofhumanplacentalexplantsbytrypanosomacruzirevealsamicrornaprofilesimilartothatseenintrophoblastdifferentiation