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Murine colon organoids as a novel model to study Trypanosoma cruzi infection and interactions with the intestinal epithelium

Chagas disease (CD) is a life-threatening illness caused by the parasite Trypanosoma cruzi (T. cruzi). With around seven million people infected worldwide and over 50,000 deaths per year, CD is a major public health issue in Latin America. The main route of transmission to humans is through a triato...

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Autores principales: Daghero, Hellen, Pagotto, Romina, Quiroga, Cristina, Medeiros, Andrea, Comini, Marcelo A., Bollati-Fogolín, Mariela
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10033869/
https://www.ncbi.nlm.nih.gov/pubmed/36968103
http://dx.doi.org/10.3389/fcimb.2023.1082524
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author Daghero, Hellen
Pagotto, Romina
Quiroga, Cristina
Medeiros, Andrea
Comini, Marcelo A.
Bollati-Fogolín, Mariela
author_facet Daghero, Hellen
Pagotto, Romina
Quiroga, Cristina
Medeiros, Andrea
Comini, Marcelo A.
Bollati-Fogolín, Mariela
author_sort Daghero, Hellen
collection PubMed
description Chagas disease (CD) is a life-threatening illness caused by the parasite Trypanosoma cruzi (T. cruzi). With around seven million people infected worldwide and over 50,000 deaths per year, CD is a major public health issue in Latin America. The main route of transmission to humans is through a triatomine bug (vector-borne), but congenital and oral transmission have also been reported. The acute phase of CD presents mild symptoms but may develop into a long-lasting chronic illness, characterized by severely impaired cardiac, digestive, and neurological functions. The intestinal tissue appears to have a key role during oral transmission and chronic infection of CD. In this immune-privileged reservoir, dormant/quiescent parasites have been suggested to contribute to disease persistence, infection relapse, and treatment failure. However, the interaction between the intestinal epithelium and T. cruzi has not been examined in depth, in part, due to the lack of in vitro models that approximate to the biological and structural complexity of this tissue. Therefore, to understand the role played by the intestinal tissue during transmission and chronic infection, physiological models resembling the organ complexity are needed. Here we addressed this issue by establishing and characterizing adult stem cell-derived colonoid infection models that are clinically relevant for CD. 3D and 2D systems of murine intestinal organoids infected with T. cruzi Dm28c (a highly virulent strain associated with oral outbreaks) were analyzed at different time points by confocal microscopy. T. cruzi was able to invade and replicate in intestinal epithelial primary cells grown as intact organoids (3D) and monolayers (2D). The permissiveness to pathogen infection differed markedly between organoids and cell lines (primate and intestinal human cell lines). So far, this represents the first evidence of the potential that these cellular systems offer for the study of host-pathogen interactions and the discovery of effective anti-chagasic drugs.
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spelling pubmed-100338692023-03-24 Murine colon organoids as a novel model to study Trypanosoma cruzi infection and interactions with the intestinal epithelium Daghero, Hellen Pagotto, Romina Quiroga, Cristina Medeiros, Andrea Comini, Marcelo A. Bollati-Fogolín, Mariela Front Cell Infect Microbiol Cellular and Infection Microbiology Chagas disease (CD) is a life-threatening illness caused by the parasite Trypanosoma cruzi (T. cruzi). With around seven million people infected worldwide and over 50,000 deaths per year, CD is a major public health issue in Latin America. The main route of transmission to humans is through a triatomine bug (vector-borne), but congenital and oral transmission have also been reported. The acute phase of CD presents mild symptoms but may develop into a long-lasting chronic illness, characterized by severely impaired cardiac, digestive, and neurological functions. The intestinal tissue appears to have a key role during oral transmission and chronic infection of CD. In this immune-privileged reservoir, dormant/quiescent parasites have been suggested to contribute to disease persistence, infection relapse, and treatment failure. However, the interaction between the intestinal epithelium and T. cruzi has not been examined in depth, in part, due to the lack of in vitro models that approximate to the biological and structural complexity of this tissue. Therefore, to understand the role played by the intestinal tissue during transmission and chronic infection, physiological models resembling the organ complexity are needed. Here we addressed this issue by establishing and characterizing adult stem cell-derived colonoid infection models that are clinically relevant for CD. 3D and 2D systems of murine intestinal organoids infected with T. cruzi Dm28c (a highly virulent strain associated with oral outbreaks) were analyzed at different time points by confocal microscopy. T. cruzi was able to invade and replicate in intestinal epithelial primary cells grown as intact organoids (3D) and monolayers (2D). The permissiveness to pathogen infection differed markedly between organoids and cell lines (primate and intestinal human cell lines). So far, this represents the first evidence of the potential that these cellular systems offer for the study of host-pathogen interactions and the discovery of effective anti-chagasic drugs. Frontiers Media S.A. 2023-03-09 /pmc/articles/PMC10033869/ /pubmed/36968103 http://dx.doi.org/10.3389/fcimb.2023.1082524 Text en Copyright © 2023 Daghero, Pagotto, Quiroga, Medeiros, Comini and Bollati-Fogolín https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cellular and Infection Microbiology
Daghero, Hellen
Pagotto, Romina
Quiroga, Cristina
Medeiros, Andrea
Comini, Marcelo A.
Bollati-Fogolín, Mariela
Murine colon organoids as a novel model to study Trypanosoma cruzi infection and interactions with the intestinal epithelium
title Murine colon organoids as a novel model to study Trypanosoma cruzi infection and interactions with the intestinal epithelium
title_full Murine colon organoids as a novel model to study Trypanosoma cruzi infection and interactions with the intestinal epithelium
title_fullStr Murine colon organoids as a novel model to study Trypanosoma cruzi infection and interactions with the intestinal epithelium
title_full_unstemmed Murine colon organoids as a novel model to study Trypanosoma cruzi infection and interactions with the intestinal epithelium
title_short Murine colon organoids as a novel model to study Trypanosoma cruzi infection and interactions with the intestinal epithelium
title_sort murine colon organoids as a novel model to study trypanosoma cruzi infection and interactions with the intestinal epithelium
topic Cellular and Infection Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10033869/
https://www.ncbi.nlm.nih.gov/pubmed/36968103
http://dx.doi.org/10.3389/fcimb.2023.1082524
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