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...
Autores principales: | , , , , , , , , |
---|---|
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 |