Caracterização da capacidade patogênica de Trypanosoma cruzi isolado em Arequipa - área endêmica do Peru

Detalhes bibliográficos
Autor(a) principal: Edward Valencia Ayala
Data de Publicação: 2017
Tipo de documento: Tese
Idioma: por
Título da fonte: Repositório Institucional da UFMG
Texto Completo: http://hdl.handle.net/1843/34799
Resumo: Trypanosoma cruzi is a complex and heterogeneous parasite, formed by six phylogenetic groups, DTU TcI to TcVI, which have great intraspecific variation, presenting different blood forms, pathogenicity, drug sensitivity, and antigenic profile, among other characteristics. In this work, we evaluated the infective or invasive capacity and antioxidant defense of a "La Joya" isolate, a region located in the west of the city of Arequipa, Peru, identified in the present work as DTU TcI. Our in vitro and in vivo experiments were carried out in a comparative perspective with Colombiana strain (DTU TcI), a virulent strain, and with CL Brener (DTU TcVI) also considered as a virulent clone of the parasite. The analysis of the proliferative capacity of each strain in in vitro infections of peritoneal macrophages obtained from BALB/c mice showed that Arequipa strain was the least infective, presenting lower rates of infection and multiplication when compared to Colombiana and CL Brener. Macrophage effectors responses were analyzed and the results showed that Arequipa strain induces higher percentages of the oxidant molecules EROs and NO when compared to Colombiana and CL Brener. The evaluation of the expression of the parasite antioxidant enzymes TcAPX, TcCPX, TcMPX, TcTrS, TcTrR, TcSodA and TcSodB in in vitro infection of macrophages showed lower levels of TcMPX, TcTrR, TcSrA, TcSodA and TcSodB by Arequipa in the initial time points when compared to the other two strains. After several attempts, infection of C57BL/6 mice with Arequipa strain was unsuccessful. This strain was then reactivated (Arequipa-RE) through triatomine passages resulting in increased expression of TcTrS, TcAPX, TcMPX and TcCPX enzymes in the first hours after in vitro macrophages infection, compared to the non-infective Arequipa. We also evaluated the experimental infections of C57BL/6 mice with each strain. The results showed that Arequipa-RE strain presented similar levels of parasitemia and tecidual parasitism as Colombiana strain, with a predominant tropism to heart and colon, although Arequipa-RE had a lower tissue parasitism compared to the Colombiana strain. CL Brener clone presented higher levels of parasitemia, mortality, and tissue parasitism in relation to the other two strains, and cardiac and skeletal muscle tropism. The evaluation of the proinflammatory cytokines INF-γ, TNF-α and IL-12 and anti-inflammatory IL-10 in the cardiac tissue of infected mice showed early induction in the synthesis of all the cytokines evaluated in the strain Arequipa infection, when compared with Colombiana and CL Brener. Our results therefore indicate low in vitro and in vivo infectivity of the Arequipa strain, with rapid immunological control of parasite replication and modulation of the immune response.
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spelling Caracterização da capacidade patogênica de Trypanosoma cruzi isolado em Arequipa - área endêmica do PeruParasitologiaTrypanosoma cruziParasitologiaTrypanosoma cruziInfecçõesTrypanosoma cruzi is a complex and heterogeneous parasite, formed by six phylogenetic groups, DTU TcI to TcVI, which have great intraspecific variation, presenting different blood forms, pathogenicity, drug sensitivity, and antigenic profile, among other characteristics. In this work, we evaluated the infective or invasive capacity and antioxidant defense of a "La Joya" isolate, a region located in the west of the city of Arequipa, Peru, identified in the present work as DTU TcI. Our in vitro and in vivo experiments were carried out in a comparative perspective with Colombiana strain (DTU TcI), a virulent strain, and with CL Brener (DTU TcVI) also considered as a virulent clone of the parasite. The analysis of the proliferative capacity of each strain in in vitro infections of peritoneal macrophages obtained from BALB/c mice showed that Arequipa strain was the least infective, presenting lower rates of infection and multiplication when compared to Colombiana and CL Brener. Macrophage effectors responses were analyzed and the results showed that Arequipa strain induces higher percentages of the oxidant molecules EROs and NO when compared to Colombiana and CL Brener. The evaluation of the expression of the parasite antioxidant enzymes TcAPX, TcCPX, TcMPX, TcTrS, TcTrR, TcSodA and TcSodB in in vitro infection of macrophages showed lower levels of TcMPX, TcTrR, TcSrA, TcSodA and TcSodB by Arequipa in the initial time points when compared to the other two strains. After several attempts, infection of C57BL/6 mice with Arequipa strain was unsuccessful. This strain was then reactivated (Arequipa-RE) through triatomine passages resulting in increased expression of TcTrS, TcAPX, TcMPX and TcCPX enzymes in the first hours after in vitro macrophages infection, compared to the non-infective Arequipa. We also evaluated the experimental infections of C57BL/6 mice with each strain. The results showed that Arequipa-RE strain presented similar levels of parasitemia and tecidual parasitism as Colombiana strain, with a predominant tropism to heart and colon, although Arequipa-RE had a lower tissue parasitism compared to the Colombiana strain. CL Brener clone presented higher levels of parasitemia, mortality, and tissue parasitism in relation to the other two strains, and cardiac and skeletal muscle tropism. The evaluation of the proinflammatory cytokines INF-γ, TNF-α and IL-12 and anti-inflammatory IL-10 in the cardiac tissue of infected mice showed early induction in the synthesis of all the cytokines evaluated in the strain Arequipa infection, when compared with Colombiana and CL Brener. Our results therefore indicate low in vitro and in vivo infectivity of the Arequipa strain, with rapid immunological control of parasite replication and modulation of the immune response.Trypanosoma cruzi é um parasito complexo e heterogêneo, formado por seis grupos filogenéticos, DTU TcI a TcVI, que possuem grande variação intraespecífica, podendo apresentar diferentes formas sanguíneas, patogenicidade, sensibilidade a drogas, perfil antigênico, dentre outras características. Neste trabalho foi avaliada a capacidade infectante ou invasiva e a defesa antioxidante de um isolado de “La Joya”, região situada ao Oeste da cidade de Arequipa, Peru, identificado neste trabalho como pertencente a DTU TcI. Nossos experimentos foram realizados em uma perspectiva comparativa com a cepa Colombiana (DTU TcI), reportada por alguns grupos como sendo virulenta, e com o clone CL Brener (DTU TcVI), também considerado um clone virulento do parasito. As análises da capacidade proliferativa in vitro no interior de macrófagos peritoneais obtidos de camundongos BALB/c mostraram que a cepa Arequipa foi a menos infectiva, apresentando menores taxas de infecção e multiplicação, quando comparada com Colombiana e CL Brener. As respostas efetoras dos macrófagos foram analisadas e os resultados mostraram que a cepa Arequipa induz maiores percentuais das moléculas oxidantes EROs e NO, quando comparada com Colombiana e CL Brener. A avaliação da expressão das enzimas antioxidantes do parasito TcAPX, TcCPX, TcMPX, TcTrS, TcTrR, TcSodA e TcSodB na infecção in vitro de macrófagos, mostrou menores níveis destas enzimas, na cepa Arequipa nos tempos iniciais da infecção quando comparada às outras duas cepas. Após insucesso na infecção experimental em camundongos C57BL/6, a cepa Arequipa foi reativada (Arequipa-RE) através de passagens no triatomíneo resultando no aumento na expressão das enzimas TcTrS, TcAPX, TcMPX e TcCPX, nas primeiras horas após infecção in vitro de macrófagos, quando comparado com a Arequipa não infectante. Avaliamos também a infecção in vivo de camundongos C57BL/6 naturalmente resistentes ao T. cruzi. Os resultados mostraram que a cepa Arequipa–RE apresentou níveis de parasitemia e parasitismo tecidual semelhante à cepa Colombiana, com tropismo preferencialmente cardíaco e no cólon, embora Arequipa-RE tenha uma menor carga parasitária tecidual quando comparado com a cepa Colombiana. A cepa CL Brener apresentou maiores níveis de parasitemia, mortalidade, e parasitismo tecidual em relação às outras duas cepas, e tropismo cardíaco e de músculo esquelético. A avaliação da expressão de citocinas pró-inflamatórias INF-γ, TNF-α e IL-12 e anti-inflamatória IL-10 no tecido cardíaco de animais infectados, mostrou indução precoce na síntese de todas as citocinas avaliadas na infecção com a cepa Arequipa-RE, em comparação com Colombiana e clone CL Brener. Nossos resultados indicam, portanto, baixa capacidade infectante in vitro e in vivo da cepa Arequipa, com um rápido controle imunológico da replicação parasitária e modulação da resposta imune.Universidade Federal de Minas GeraisBrasilICB - INSTITUTO DE CIÊNCIAS BIOLOGICASPrograma de Pós-Graduação em ParasitologiaUFMGDaniella Castanheira Bartholomeuhttp://lattes.cnpq.br/0345205615498048Denise da Silveira LemosFernanda Fortes de AraújoPolicarpo Ademar Sales JúniorLuciana de Oliveira AndradeMaurício Roberto Viana Sant'AnnaEdward Valencia Ayala2021-01-20T18:14:53Z2021-01-20T18:14:53Z2017-05-19info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisapplication/pdfhttp://hdl.handle.net/1843/34799porhttp://creativecommons.org/licenses/by-nc-nd/3.0/pt/info:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFMGinstname:Universidade Federal de Minas Gerais (UFMG)instacron:UFMG2021-01-20T18:14:53Zoai:repositorio.ufmg.br:1843/34799Repositório InstitucionalPUBhttps://repositorio.ufmg.br/oairepositorio@ufmg.bropendoar:2021-01-20T18:14:53Repositório Institucional da UFMG - Universidade Federal de Minas Gerais (UFMG)false
dc.title.none.fl_str_mv Caracterização da capacidade patogênica de Trypanosoma cruzi isolado em Arequipa - área endêmica do Peru
title Caracterização da capacidade patogênica de Trypanosoma cruzi isolado em Arequipa - área endêmica do Peru
spellingShingle Caracterização da capacidade patogênica de Trypanosoma cruzi isolado em Arequipa - área endêmica do Peru
Edward Valencia Ayala
Parasitologia
Trypanosoma cruzi
Parasitologia
Trypanosoma cruzi
Infecções
title_short Caracterização da capacidade patogênica de Trypanosoma cruzi isolado em Arequipa - área endêmica do Peru
title_full Caracterização da capacidade patogênica de Trypanosoma cruzi isolado em Arequipa - área endêmica do Peru
title_fullStr Caracterização da capacidade patogênica de Trypanosoma cruzi isolado em Arequipa - área endêmica do Peru
title_full_unstemmed Caracterização da capacidade patogênica de Trypanosoma cruzi isolado em Arequipa - área endêmica do Peru
title_sort Caracterização da capacidade patogênica de Trypanosoma cruzi isolado em Arequipa - área endêmica do Peru
author Edward Valencia Ayala
author_facet Edward Valencia Ayala
author_role author
dc.contributor.none.fl_str_mv Daniella Castanheira Bartholomeu
http://lattes.cnpq.br/0345205615498048
Denise da Silveira Lemos
Fernanda Fortes de Araújo
Policarpo Ademar Sales Júnior
Luciana de Oliveira Andrade
Maurício Roberto Viana Sant'Anna
dc.contributor.author.fl_str_mv Edward Valencia Ayala
dc.subject.por.fl_str_mv Parasitologia
Trypanosoma cruzi
Parasitologia
Trypanosoma cruzi
Infecções
topic Parasitologia
Trypanosoma cruzi
Parasitologia
Trypanosoma cruzi
Infecções
description Trypanosoma cruzi is a complex and heterogeneous parasite, formed by six phylogenetic groups, DTU TcI to TcVI, which have great intraspecific variation, presenting different blood forms, pathogenicity, drug sensitivity, and antigenic profile, among other characteristics. In this work, we evaluated the infective or invasive capacity and antioxidant defense of a "La Joya" isolate, a region located in the west of the city of Arequipa, Peru, identified in the present work as DTU TcI. Our in vitro and in vivo experiments were carried out in a comparative perspective with Colombiana strain (DTU TcI), a virulent strain, and with CL Brener (DTU TcVI) also considered as a virulent clone of the parasite. The analysis of the proliferative capacity of each strain in in vitro infections of peritoneal macrophages obtained from BALB/c mice showed that Arequipa strain was the least infective, presenting lower rates of infection and multiplication when compared to Colombiana and CL Brener. Macrophage effectors responses were analyzed and the results showed that Arequipa strain induces higher percentages of the oxidant molecules EROs and NO when compared to Colombiana and CL Brener. The evaluation of the expression of the parasite antioxidant enzymes TcAPX, TcCPX, TcMPX, TcTrS, TcTrR, TcSodA and TcSodB in in vitro infection of macrophages showed lower levels of TcMPX, TcTrR, TcSrA, TcSodA and TcSodB by Arequipa in the initial time points when compared to the other two strains. After several attempts, infection of C57BL/6 mice with Arequipa strain was unsuccessful. This strain was then reactivated (Arequipa-RE) through triatomine passages resulting in increased expression of TcTrS, TcAPX, TcMPX and TcCPX enzymes in the first hours after in vitro macrophages infection, compared to the non-infective Arequipa. We also evaluated the experimental infections of C57BL/6 mice with each strain. The results showed that Arequipa-RE strain presented similar levels of parasitemia and tecidual parasitism as Colombiana strain, with a predominant tropism to heart and colon, although Arequipa-RE had a lower tissue parasitism compared to the Colombiana strain. CL Brener clone presented higher levels of parasitemia, mortality, and tissue parasitism in relation to the other two strains, and cardiac and skeletal muscle tropism. The evaluation of the proinflammatory cytokines INF-γ, TNF-α and IL-12 and anti-inflammatory IL-10 in the cardiac tissue of infected mice showed early induction in the synthesis of all the cytokines evaluated in the strain Arequipa infection, when compared with Colombiana and CL Brener. Our results therefore indicate low in vitro and in vivo infectivity of the Arequipa strain, with rapid immunological control of parasite replication and modulation of the immune response.
publishDate 2017
dc.date.none.fl_str_mv 2017-05-19
2021-01-20T18:14:53Z
2021-01-20T18:14:53Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/doctoralThesis
format doctoralThesis
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/1843/34799
url http://hdl.handle.net/1843/34799
dc.language.iso.fl_str_mv por
language por
dc.rights.driver.fl_str_mv http://creativecommons.org/licenses/by-nc-nd/3.0/pt/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-nd/3.0/pt/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Universidade Federal de Minas Gerais
Brasil
ICB - INSTITUTO DE CIÊNCIAS BIOLOGICAS
Programa de Pós-Graduação em Parasitologia
UFMG
publisher.none.fl_str_mv Universidade Federal de Minas Gerais
Brasil
ICB - INSTITUTO DE CIÊNCIAS BIOLOGICAS
Programa de Pós-Graduação em Parasitologia
UFMG
dc.source.none.fl_str_mv reponame:Repositório Institucional da UFMG
instname:Universidade Federal de Minas Gerais (UFMG)
instacron:UFMG
instname_str Universidade Federal de Minas Gerais (UFMG)
instacron_str UFMG
institution UFMG
reponame_str Repositório Institucional da UFMG
collection Repositório Institucional da UFMG
repository.name.fl_str_mv Repositório Institucional da UFMG - Universidade Federal de Minas Gerais (UFMG)
repository.mail.fl_str_mv repositorio@ufmg.br
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