Differential Modulation of Mouse Heart Gene Expression by Infection With Two Trypanosoma cruzi Strains: A Transcriptome Analysis

The protozoan Trypanosoma cruzi (T. cruzi) is a well-adapted parasite to mammalian hosts and the pathogen of Chagas disease in humans. As both host and T. cruzi are highly genetically diverse, many variables come into play during infection, making disease outcomes difficult to predict. One important...

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Main Authors: Tiago Bruno Rezende de Castro, Maria Cecilia Campos Canesso, Mariana Boroni, Daniela Ferreira Chame, Daniela de Laet Souza, Nayara Evelin de Toledo, Eric Birelli Tahara, Sergio Danilo Pena, Carlos Renato Machado, Egler Chiari, Andrea Macedo, Gloria Regina Franco
Format: Article
Language:English
Published: Frontiers Media S.A. 2020-09-01
Series:Frontiers in Genetics
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fgene.2020.01031/full
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spelling doaj-f6211f19dcf042059e98a03ce934c7822020-11-25T03:19:57ZengFrontiers Media S.A.Frontiers in Genetics1664-80212020-09-011110.3389/fgene.2020.01031549116Differential Modulation of Mouse Heart Gene Expression by Infection With Two Trypanosoma cruzi Strains: A Transcriptome AnalysisTiago Bruno Rezende de Castro0Maria Cecilia Campos Canesso1Mariana Boroni2Daniela Ferreira Chame3Daniela de Laet Souza4Nayara Evelin de Toledo5Eric Birelli Tahara6Sergio Danilo Pena7Carlos Renato Machado8Egler Chiari9Andrea Macedo10Gloria Regina Franco11Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, UFMG, Belo Horizonte, BrazilDepartamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, UFMG, Belo Horizonte, BrazilLaboratório de Bioinformática e Biologia Computacional, Centro de Pesquisas, Instituto Nacional de Câncer, Rio de Janeiro, BrazilDepartamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, UFMG, Belo Horizonte, BrazilDepartamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, UFMG, Belo Horizonte, BrazilDepartamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, UFMG, Belo Horizonte, BrazilDepartamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, UFMG, Belo Horizonte, BrazilDepartamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, UFMG, Belo Horizonte, BrazilDepartamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, UFMG, Belo Horizonte, BrazilDepartamento de Parasitologia, Universidade Federal de Minas Gerais, UFMG, Belo Horizonte, BrazilDepartamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, UFMG, Belo Horizonte, BrazilDepartamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, UFMG, Belo Horizonte, BrazilThe protozoan Trypanosoma cruzi (T. cruzi) is a well-adapted parasite to mammalian hosts and the pathogen of Chagas disease in humans. As both host and T. cruzi are highly genetically diverse, many variables come into play during infection, making disease outcomes difficult to predict. One important challenge in the field of Chagas disease research is determining the main factors leading to parasite establishment in the chronic stage in some organs, mainly the heart and/or digestive system. Our group previously showed that distinct strains of T. cruzi (JG and Col1.7G2) acquired differential tissue distribution in the chronic stage in dually infected BALB/c mice. To investigate changes in the host triggered by the two distinct T. cruzi strains, we assessed the gene expression profiles of BALB/c mouse hearts infected with either JG, Col1.7G2 or an equivalent mixture of both parasites during the initial phase of infection. This study demonstrates the clear differences in modulation of host gene expression by both parasites. Col1.7G2 strongly activated Th1-polarized immune signature genes, whereas JG caused only minor activation of the host immune response. Moreover, JG strongly reduced the expression of genes encoding ribosomal proteins and mitochondrial proteins related to the electron transport chain. Interestingly, the evaluation of gene expression in mice inoculated with a mixture of the parasites produced expression profiles with both up- and downregulated genes, indicating the coexistence of both parasite strains in the heart during the acute phase. This study suggests that different strains of T. cruzi may be distinguished by their efficiency in activating the immune system, modulating host energy metabolism and reactive oxygen species production and decreasing protein synthesis during early infection, which may be crucial for parasite persistence in specific organs.https://www.frontiersin.org/article/10.3389/fgene.2020.01031/fullTrypanosoma cruzihost-parasite interactionheart transcriptomeimmune systemdifferential gene expression
collection DOAJ
language English
format Article
sources DOAJ
author Tiago Bruno Rezende de Castro
Maria Cecilia Campos Canesso
Mariana Boroni
Daniela Ferreira Chame
Daniela de Laet Souza
Nayara Evelin de Toledo
Eric Birelli Tahara
Sergio Danilo Pena
Carlos Renato Machado
Egler Chiari
Andrea Macedo
Gloria Regina Franco
spellingShingle Tiago Bruno Rezende de Castro
Maria Cecilia Campos Canesso
Mariana Boroni
Daniela Ferreira Chame
Daniela de Laet Souza
Nayara Evelin de Toledo
Eric Birelli Tahara
Sergio Danilo Pena
Carlos Renato Machado
Egler Chiari
Andrea Macedo
Gloria Regina Franco
Differential Modulation of Mouse Heart Gene Expression by Infection With Two Trypanosoma cruzi Strains: A Transcriptome Analysis
Frontiers in Genetics
Trypanosoma cruzi
host-parasite interaction
heart transcriptome
immune system
differential gene expression
author_facet Tiago Bruno Rezende de Castro
Maria Cecilia Campos Canesso
Mariana Boroni
Daniela Ferreira Chame
Daniela de Laet Souza
Nayara Evelin de Toledo
Eric Birelli Tahara
Sergio Danilo Pena
Carlos Renato Machado
Egler Chiari
Andrea Macedo
Gloria Regina Franco
author_sort Tiago Bruno Rezende de Castro
title Differential Modulation of Mouse Heart Gene Expression by Infection With Two Trypanosoma cruzi Strains: A Transcriptome Analysis
title_short Differential Modulation of Mouse Heart Gene Expression by Infection With Two Trypanosoma cruzi Strains: A Transcriptome Analysis
title_full Differential Modulation of Mouse Heart Gene Expression by Infection With Two Trypanosoma cruzi Strains: A Transcriptome Analysis
title_fullStr Differential Modulation of Mouse Heart Gene Expression by Infection With Two Trypanosoma cruzi Strains: A Transcriptome Analysis
title_full_unstemmed Differential Modulation of Mouse Heart Gene Expression by Infection With Two Trypanosoma cruzi Strains: A Transcriptome Analysis
title_sort differential modulation of mouse heart gene expression by infection with two trypanosoma cruzi strains: a transcriptome analysis
publisher Frontiers Media S.A.
series Frontiers in Genetics
issn 1664-8021
publishDate 2020-09-01
description The protozoan Trypanosoma cruzi (T. cruzi) is a well-adapted parasite to mammalian hosts and the pathogen of Chagas disease in humans. As both host and T. cruzi are highly genetically diverse, many variables come into play during infection, making disease outcomes difficult to predict. One important challenge in the field of Chagas disease research is determining the main factors leading to parasite establishment in the chronic stage in some organs, mainly the heart and/or digestive system. Our group previously showed that distinct strains of T. cruzi (JG and Col1.7G2) acquired differential tissue distribution in the chronic stage in dually infected BALB/c mice. To investigate changes in the host triggered by the two distinct T. cruzi strains, we assessed the gene expression profiles of BALB/c mouse hearts infected with either JG, Col1.7G2 or an equivalent mixture of both parasites during the initial phase of infection. This study demonstrates the clear differences in modulation of host gene expression by both parasites. Col1.7G2 strongly activated Th1-polarized immune signature genes, whereas JG caused only minor activation of the host immune response. Moreover, JG strongly reduced the expression of genes encoding ribosomal proteins and mitochondrial proteins related to the electron transport chain. Interestingly, the evaluation of gene expression in mice inoculated with a mixture of the parasites produced expression profiles with both up- and downregulated genes, indicating the coexistence of both parasite strains in the heart during the acute phase. This study suggests that different strains of T. cruzi may be distinguished by their efficiency in activating the immune system, modulating host energy metabolism and reactive oxygen species production and decreasing protein synthesis during early infection, which may be crucial for parasite persistence in specific organs.
topic Trypanosoma cruzi
host-parasite interaction
heart transcriptome
immune system
differential gene expression
url https://www.frontiersin.org/article/10.3389/fgene.2020.01031/full
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