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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Main Authors: Renata Watanabe Costa, Marina Ferreira Batista, Isabela Meneghelli, 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
Format: Article
Language:English
Published: Frontiers Media S.A. 2020-08-01
Series:Frontiers in Immunology
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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.
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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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