Comparative Analysis of the Secretome and Interactome of Trypanosoma cruzi and Trypanosoma rangeli Reveals Species Specific Immune Response Modulating Proteins
Chagas disease, a zoonosis caused by the flagellate protozoan Trypanosoma cruzi, is a chronic and systemic parasitic infection that affects ~5–7 million people worldwide, mainly in Latin America. Chagas disease is an emerging public health problem due to the lack of vaccines and effective treatments...
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Frontiers Media S.A.
2020-08-01
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Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2020.01774/full |
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author | Renata Watanabe Costa Marina Ferreira Batista Isabela Meneghelli Ramon Oliveira Vidal Ramon Oliveira Vidal Carlos Alcides Nájera Ana Clara Mendes Izabela Augusta Andrade-Lima José Franco da Silveira Luciano Rodrigo Lopes Ludmila Rodrigues Pinto Ferreira Fernando Antoneli Diana Bahia Diana Bahia |
author_facet | Renata Watanabe Costa Marina Ferreira Batista Isabela Meneghelli Ramon Oliveira Vidal Ramon Oliveira Vidal Carlos Alcides Nájera Ana Clara Mendes Izabela Augusta Andrade-Lima José Franco da Silveira Luciano Rodrigo Lopes Ludmila Rodrigues Pinto Ferreira Fernando Antoneli Diana Bahia Diana Bahia |
author_sort | Renata Watanabe Costa |
collection | DOAJ |
description | Chagas disease, a zoonosis caused by the flagellate protozoan Trypanosoma cruzi, is a chronic and systemic parasitic infection that affects ~5–7 million people worldwide, mainly in Latin America. Chagas disease is an emerging public health problem due to the lack of vaccines and effective treatments. According to recent studies, several T. cruzi secreted proteins interact with the human host during cell invasion. Moreover, some comparative studies with T. rangeli, which is non-pathogenic in humans, have been performed to identify proteins directly involved in the pathogenesis of the disease. In this study, we present an integrated analysis of canonical putative secreted proteins (PSPs) from both species. Additionally, we propose an interactome with human host and gene family clusters, and a phylogenetic inference of a selected protein. In total, we identified 322 exclusively PSPs in T. cruzi and 202 in T. rangeli. Among the PSPs identified in T. cruzi, we found several trans-sialidases, mucins, MASPs, proteins with phospholipase 2 domains (PLA2-like), and proteins with Hsp70 domains (Hsp70-like) which have been previously characterized and demonstrated to be related to T. cruzi virulence. PSPs found in T. rangeli were related to protozoan metabolism, specifically carboxylases and phosphatases. Furthermore, we also identified PSPs that may interact with the human immune system, including heat shock and MASP proteins, but in a lower number compared to T. cruzi. Interestingly, we describe a hypothetical hybrid interactome of PSPs which reveals that T. cruzi secreted molecules may be down-regulating IL-17 whilst T. rangeli may enhance the production of IL-15. These results will pave the way for a better understanding of the pathophysiology of Chagas disease and may ultimately lead to the identification of molecular targets, such as key PSPs, that could be used to minimize the health outcomes of Chagas disease by modulating the immune response triggered by T. cruzi infection. |
first_indexed | 2024-12-11T16:10:26Z |
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last_indexed | 2024-12-11T16:10:26Z |
publishDate | 2020-08-01 |
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spelling | doaj.art-b286cd6422b2482f9082c6a92939467e2022-12-22T00:59:05ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-08-011110.3389/fimmu.2020.01774550289Comparative Analysis of the Secretome and Interactome of Trypanosoma cruzi and Trypanosoma rangeli Reveals Species Specific Immune Response Modulating ProteinsRenata Watanabe Costa0Marina Ferreira Batista1Isabela Meneghelli2Ramon Oliveira Vidal3Ramon Oliveira Vidal4Carlos Alcides Nájera5Ana Clara Mendes6Izabela Augusta Andrade-Lima7José Franco da Silveira8Luciano Rodrigo Lopes9Ludmila Rodrigues Pinto Ferreira10Fernando Antoneli11Diana Bahia12Diana Bahia13Departamento de Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, BrazilDepartamento de Genética, Ecologia e Evolução, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, BrazilDepartamento de Genética, Ecologia e Evolução, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, BrazilThe Berlin Institute for Medical Systems Biology-Max Delbrück Center for Molecular Medicine in the Helmholtz Association in Berlin, Berlin, GermanyLaboratorio Nacional de Biociências (LNBio), Campinas, São Paulo, BrazilDepartamento de Genética, Ecologia e Evolução, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, BrazilDepartamento de Genética, Ecologia e Evolução, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, BrazilDepartamento de Genética, Ecologia e Evolução, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, BrazilDepartamento de Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, BrazilDepartamento de Informática em Saúde, Universidade Federal de São Paulo, São Paulo, BrazilRNA Systems Biology Lab (RSBL), Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, BrazilDepartamento de Informática em Saúde, Universidade Federal de São Paulo, São Paulo, BrazilDepartamento de Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, BrazilDepartamento de Genética, Ecologia e Evolução, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, BrazilChagas disease, a zoonosis caused by the flagellate protozoan Trypanosoma cruzi, is a chronic and systemic parasitic infection that affects ~5–7 million people worldwide, mainly in Latin America. Chagas disease is an emerging public health problem due to the lack of vaccines and effective treatments. According to recent studies, several T. cruzi secreted proteins interact with the human host during cell invasion. Moreover, some comparative studies with T. rangeli, which is non-pathogenic in humans, have been performed to identify proteins directly involved in the pathogenesis of the disease. In this study, we present an integrated analysis of canonical putative secreted proteins (PSPs) from both species. Additionally, we propose an interactome with human host and gene family clusters, and a phylogenetic inference of a selected protein. In total, we identified 322 exclusively PSPs in T. cruzi and 202 in T. rangeli. Among the PSPs identified in T. cruzi, we found several trans-sialidases, mucins, MASPs, proteins with phospholipase 2 domains (PLA2-like), and proteins with Hsp70 domains (Hsp70-like) which have been previously characterized and demonstrated to be related to T. cruzi virulence. PSPs found in T. rangeli were related to protozoan metabolism, specifically carboxylases and phosphatases. Furthermore, we also identified PSPs that may interact with the human immune system, including heat shock and MASP proteins, but in a lower number compared to T. cruzi. Interestingly, we describe a hypothetical hybrid interactome of PSPs which reveals that T. cruzi secreted molecules may be down-regulating IL-17 whilst T. rangeli may enhance the production of IL-15. These results will pave the way for a better understanding of the pathophysiology of Chagas disease and may ultimately lead to the identification of molecular targets, such as key PSPs, that could be used to minimize the health outcomes of Chagas disease by modulating the immune response triggered by T. cruzi infection.https://www.frontiersin.org/article/10.3389/fimmu.2020.01774/fullinteractomesecretomeIL17IL15Trypanosoma rangeliTrypanosoma cruzi |
spellingShingle | Renata Watanabe Costa Marina Ferreira Batista Isabela Meneghelli Ramon Oliveira Vidal Ramon Oliveira Vidal Carlos Alcides Nájera Ana Clara Mendes Izabela Augusta Andrade-Lima José Franco da Silveira Luciano Rodrigo Lopes Ludmila Rodrigues Pinto Ferreira Fernando Antoneli Diana Bahia Diana Bahia Comparative Analysis of the Secretome and Interactome of Trypanosoma cruzi and Trypanosoma rangeli Reveals Species Specific Immune Response Modulating Proteins Frontiers in Immunology interactome secretome IL17 IL15 Trypanosoma rangeli Trypanosoma cruzi |
title | Comparative Analysis of the Secretome and Interactome of Trypanosoma cruzi and Trypanosoma rangeli Reveals Species Specific Immune Response Modulating Proteins |
title_full | Comparative Analysis of the Secretome and Interactome of Trypanosoma cruzi and Trypanosoma rangeli Reveals Species Specific Immune Response Modulating Proteins |
title_fullStr | Comparative Analysis of the Secretome and Interactome of Trypanosoma cruzi and Trypanosoma rangeli Reveals Species Specific Immune Response Modulating Proteins |
title_full_unstemmed | Comparative Analysis of the Secretome and Interactome of Trypanosoma cruzi and Trypanosoma rangeli Reveals Species Specific Immune Response Modulating Proteins |
title_short | Comparative Analysis of the Secretome and Interactome of Trypanosoma cruzi and Trypanosoma rangeli Reveals Species Specific Immune Response Modulating Proteins |
title_sort | comparative analysis of the secretome and interactome of trypanosoma cruzi and trypanosoma rangeli reveals species specific immune response modulating proteins |
topic | interactome secretome IL17 IL15 Trypanosoma rangeli Trypanosoma cruzi |
url | https://www.frontiersin.org/article/10.3389/fimmu.2020.01774/full |
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