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Host Genetics Background Influence in the Intragastric Trypanosoma cruzi Infection

BACKGROUND: Considering the complexity of the factors involved in the immunopathology of Chagas disease, which influence the Chagas’ disease pathogenesis, anti-T. cruzi immune response, and chemotherapy outcome, further studies are needed to improve our understanding about these relationships. On th...

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Autores principales: Domingues, Carolina Salles, Cardoso, Flávia de Oliveira, Hardoim, Daiana de Jesus, Pelajo-Machado, Marcelo, Bertho, Alvaro Luiz, Calabrese, Kátia da Silva
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7732431/
https://www.ncbi.nlm.nih.gov/pubmed/33329529
http://dx.doi.org/10.3389/fimmu.2020.566476
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author Domingues, Carolina Salles
Cardoso, Flávia de Oliveira
Hardoim, Daiana de Jesus
Pelajo-Machado, Marcelo
Bertho, Alvaro Luiz
Calabrese, Kátia da Silva
author_facet Domingues, Carolina Salles
Cardoso, Flávia de Oliveira
Hardoim, Daiana de Jesus
Pelajo-Machado, Marcelo
Bertho, Alvaro Luiz
Calabrese, Kátia da Silva
author_sort Domingues, Carolina Salles
collection PubMed
description BACKGROUND: Considering the complexity of the factors involved in the immunopathology of Chagas disease, which influence the Chagas’ disease pathogenesis, anti-T. cruzi immune response, and chemotherapy outcome, further studies are needed to improve our understanding about these relationships. On this way, in this article we analyzed the host genetic influence on hematological, histopathological and immunological aspects after T. cruzi infection. METHODS: BALB/c and A mice were intragastrically infected with T. cruzi SC2005 strain, isolated from a patient of an outbreak of Chagas disease. Parameters such as parasite load, survival rates, cytokines production, macrophages, T and B cell frequencies, and histopathology analysis were carried out. RESULTS: BALB/c mice presented higher parasitemia and mortality rates than A mice. Both mouse lineages exhibited hematological alterations suggestive of microcytic hypochromic anemia and histopathological alterations in stomach, heart and liver. The increase of CD8(+) T cells, in heart, liver and blood, and the increase of CD19(+) B cells, in liver, associated with a high level of proinflammatory cytokines (IL-6, TNF-α, IFN-γ), confer a resistance profile to the host. Although BALB/c animals exhibited the same findings observed in A mice, the response to infection occurred later, after a considerable parasitemia increase. By developing an early response to the infection, A mice were found to be less susceptible to T. cruzi SC2005 infection. CONCLUSIONS: Host genetics background shaping the response to infection. The early development of a cytotoxic cellular response profile with the production of proinflammatory cytokines is important to lead a less severe manifestation of Chagas disease.
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spelling pubmed-77324312020-12-15 Host Genetics Background Influence in the Intragastric Trypanosoma cruzi Infection Domingues, Carolina Salles Cardoso, Flávia de Oliveira Hardoim, Daiana de Jesus Pelajo-Machado, Marcelo Bertho, Alvaro Luiz Calabrese, Kátia da Silva Front Immunol Immunology BACKGROUND: Considering the complexity of the factors involved in the immunopathology of Chagas disease, which influence the Chagas’ disease pathogenesis, anti-T. cruzi immune response, and chemotherapy outcome, further studies are needed to improve our understanding about these relationships. On this way, in this article we analyzed the host genetic influence on hematological, histopathological and immunological aspects after T. cruzi infection. METHODS: BALB/c and A mice were intragastrically infected with T. cruzi SC2005 strain, isolated from a patient of an outbreak of Chagas disease. Parameters such as parasite load, survival rates, cytokines production, macrophages, T and B cell frequencies, and histopathology analysis were carried out. RESULTS: BALB/c mice presented higher parasitemia and mortality rates than A mice. Both mouse lineages exhibited hematological alterations suggestive of microcytic hypochromic anemia and histopathological alterations in stomach, heart and liver. The increase of CD8(+) T cells, in heart, liver and blood, and the increase of CD19(+) B cells, in liver, associated with a high level of proinflammatory cytokines (IL-6, TNF-α, IFN-γ), confer a resistance profile to the host. Although BALB/c animals exhibited the same findings observed in A mice, the response to infection occurred later, after a considerable parasitemia increase. By developing an early response to the infection, A mice were found to be less susceptible to T. cruzi SC2005 infection. CONCLUSIONS: Host genetics background shaping the response to infection. The early development of a cytotoxic cellular response profile with the production of proinflammatory cytokines is important to lead a less severe manifestation of Chagas disease. Frontiers Media S.A. 2020-11-24 /pmc/articles/PMC7732431/ /pubmed/33329529 http://dx.doi.org/10.3389/fimmu.2020.566476 Text en Copyright © 2020 Domingues, Cardoso, Hardoim, Pelajo-Machado, Bertho and Calabrese http://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 Immunology
Domingues, Carolina Salles
Cardoso, Flávia de Oliveira
Hardoim, Daiana de Jesus
Pelajo-Machado, Marcelo
Bertho, Alvaro Luiz
Calabrese, Kátia da Silva
Host Genetics Background Influence in the Intragastric Trypanosoma cruzi Infection
title Host Genetics Background Influence in the Intragastric Trypanosoma cruzi Infection
title_full Host Genetics Background Influence in the Intragastric Trypanosoma cruzi Infection
title_fullStr Host Genetics Background Influence in the Intragastric Trypanosoma cruzi Infection
title_full_unstemmed Host Genetics Background Influence in the Intragastric Trypanosoma cruzi Infection
title_short Host Genetics Background Influence in the Intragastric Trypanosoma cruzi Infection
title_sort host genetics background influence in the intragastric trypanosoma cruzi infection
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7732431/
https://www.ncbi.nlm.nih.gov/pubmed/33329529
http://dx.doi.org/10.3389/fimmu.2020.566476
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