Absence of CD4(+) T Lymphocytes, CD8(+) T Lymphocytes, or B Lymphocytes Has Different Effects on the Efficacy of Posaconazole and Benznidazole in Treatment of Experimental Acute Trypanosoma cruzi Infection

Detalhes bibliográficos
Autor(a) principal: Ferraz, Marcela Lencine
Data de Publicação: 2009
Outros Autores: Gazzinelli, Ricardo Tostes, Alves, Rosana de Oliveira, Urbina, Julio A, Romanha, Alvaro José
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/58342
Resumo: Fundação Oswaldo Cruz. Centro de Pesquisa René Rachou. Laboratório de Parasitologia Celular e Molecular. Belo Horizonte, MG, Brazil.
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spelling Ferraz, Marcela LencineGazzinelli, Ricardo TostesAlves, Rosana de OliveiraUrbina, Julio ARomanha, Alvaro José2023-05-12T12:57:34Z2023-05-12T12:57:34Z2009FERRAZ, Marcela Lencine et al. Absence of CD4+ T lymphocytes, CD8+ T lymphocytes, or B lymphocytes has different effects on the efficacy of posaconazole and benznidazole in treatment of experimental acute Trypanosoma cruzi infection. Antimicrob Agents Chemother., v. 53, n. 1, p. 174-179, 2009. doi: 10.1128/AAC.00779-08.0066-4804https://www.arca.fiocruz.br/handle/icict/5834210.1128/AAC.00779-08engAmerican Society for MicrobiologyAbsence of CD4(+) T Lymphocytes, CD8(+) T Lymphocytes, or B Lymphocytes Has Different Effects on the Efficacy of Posaconazole and Benznidazole in Treatment of Experimental Acute Trypanosoma cruzi Infectioninfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Centro de Pesquisa René Rachou. Laboratório de Parasitologia Celular e Molecular. Belo Horizonte, MG, Brazil.Fundação Oswaldo Cruz. Centro de Pesquisa René Rachou. Laboratorio de Imunopatologia. Belo Horizonte, MG, Brazil/Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, BrazilFundação Oswaldo Cruz. Centro de Pesquisa René Rachou. Laboratório de Parasitologia Celular e Molecular. Belo Horizonte, MG, Brazil.Laboratório de Química Biológica. Centro de Biofísica y Bioquímica. Instituto Venezolano de Investigaciones Científicas. Caracas, VenezuelaFundação Oswaldo Cruz. Centro de Pesquisa René Rachou. Laboratório de Parasitologia Celular e Molecular. Belo Horizonte, MG, Brazil.We investigated the influence of CD4(+) T lymphocytes, CD8(+) T lymphocytes, and B lymphocytes on the efficacy of posaconazole (POS) and the reference drug benznidazole (BZ) during treatment of acute Trypanosoma cruzi infection in a murine model. Wild-type mice infected with T. cruzi and treated with POS or BZ presented no parasitemia, 100% survival, and 86 to 89% cure rates, defined as the percentages of animals with negative hemocultures at the end of the observation period. CD4(+)-T-lymphocyte-knockout (KO) mice infected with T. cruzi and treated with BZ or POS controlled parasitemia during treatment, although circulating parasites reappeared after drug pressure cessation, leading to only a 6% survival rate and no cure. CD8(+)-Tlymphocyte-KO mice infected with T. cruzi and treated with POS or BZ had intermediate results, displaying discrete parasitemia after the treatment was ended, 81 and 86% survival, and cure rates of 31 and 66%, respectively. B-lymphocyte-KO mice infected with T. cruzi and treated with BZ relapsed with parasitemia 1 week after the end of treatment and had a 67% survival rate and only a 22% cure rate. In contrast, the activity of POS was much less affected in these animals, with permanent suppression of parasitemia, 100% survival, and a 71% cure rate. Our results demonstrate that abrogation of different lymphocytes' activities has distinct effects on the efficacy of POS and BZ in this experimental model, probably reflecting different parasite stages preferentially targeted by the two drugs and distinct cooperation patterns with the host immune systeminfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZORIGINALAbsence of CD4+ T lymphocytes, CD8+ T.pdfAbsence of CD4+ T lymphocytes, CD8+ T.pdfapplication/pdf307568https://www.arca.fiocruz.br/bitstream/icict/58342/2/Absence%20of%20CD4%2b%20T%20lymphocytes%2c%20CD8%2b%20T.pdf5d4081b5a31ac4fcaf3f86357bb92598MD52LICENSElicense.txttext/plain1748https://www.arca.fiocruz.br/bitstream/icict/58342/1/license.txt8a4605be74aa9ea9d79846c1fba20a33MD51icict/583422023-05-12 09:57:36.055oai:www.arca.fiocruz.br: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Repositório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352023-05-12T12:57:36Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false
dc.title.en_US.fl_str_mv Absence of CD4(+) T Lymphocytes, CD8(+) T Lymphocytes, or B Lymphocytes Has Different Effects on the Efficacy of Posaconazole and Benznidazole in Treatment of Experimental Acute Trypanosoma cruzi Infection
title Absence of CD4(+) T Lymphocytes, CD8(+) T Lymphocytes, or B Lymphocytes Has Different Effects on the Efficacy of Posaconazole and Benznidazole in Treatment of Experimental Acute Trypanosoma cruzi Infection
spellingShingle Absence of CD4(+) T Lymphocytes, CD8(+) T Lymphocytes, or B Lymphocytes Has Different Effects on the Efficacy of Posaconazole and Benznidazole in Treatment of Experimental Acute Trypanosoma cruzi Infection
Ferraz, Marcela Lencine
title_short Absence of CD4(+) T Lymphocytes, CD8(+) T Lymphocytes, or B Lymphocytes Has Different Effects on the Efficacy of Posaconazole and Benznidazole in Treatment of Experimental Acute Trypanosoma cruzi Infection
title_full Absence of CD4(+) T Lymphocytes, CD8(+) T Lymphocytes, or B Lymphocytes Has Different Effects on the Efficacy of Posaconazole and Benznidazole in Treatment of Experimental Acute Trypanosoma cruzi Infection
title_fullStr Absence of CD4(+) T Lymphocytes, CD8(+) T Lymphocytes, or B Lymphocytes Has Different Effects on the Efficacy of Posaconazole and Benznidazole in Treatment of Experimental Acute Trypanosoma cruzi Infection
title_full_unstemmed Absence of CD4(+) T Lymphocytes, CD8(+) T Lymphocytes, or B Lymphocytes Has Different Effects on the Efficacy of Posaconazole and Benznidazole in Treatment of Experimental Acute Trypanosoma cruzi Infection
title_sort Absence of CD4(+) T Lymphocytes, CD8(+) T Lymphocytes, or B Lymphocytes Has Different Effects on the Efficacy of Posaconazole and Benznidazole in Treatment of Experimental Acute Trypanosoma cruzi Infection
author Ferraz, Marcela Lencine
author_facet Ferraz, Marcela Lencine
Gazzinelli, Ricardo Tostes
Alves, Rosana de Oliveira
Urbina, Julio A
Romanha, Alvaro José
author_role author
author2 Gazzinelli, Ricardo Tostes
Alves, Rosana de Oliveira
Urbina, Julio A
Romanha, Alvaro José
author2_role author
author
author
author
dc.contributor.author.fl_str_mv Ferraz, Marcela Lencine
Gazzinelli, Ricardo Tostes
Alves, Rosana de Oliveira
Urbina, Julio A
Romanha, Alvaro José
description Fundação Oswaldo Cruz. Centro de Pesquisa René Rachou. Laboratório de Parasitologia Celular e Molecular. Belo Horizonte, MG, Brazil.
publishDate 2009
dc.date.issued.fl_str_mv 2009
dc.date.accessioned.fl_str_mv 2023-05-12T12:57:34Z
dc.date.available.fl_str_mv 2023-05-12T12:57:34Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
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status_str publishedVersion
dc.identifier.citation.fl_str_mv FERRAZ, Marcela Lencine et al. Absence of CD4+ T lymphocytes, CD8+ T lymphocytes, or B lymphocytes has different effects on the efficacy of posaconazole and benznidazole in treatment of experimental acute Trypanosoma cruzi infection. Antimicrob Agents Chemother., v. 53, n. 1, p. 174-179, 2009. doi: 10.1128/AAC.00779-08.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/58342
dc.identifier.issn.en_US.fl_str_mv 0066-4804
dc.identifier.doi.none.fl_str_mv 10.1128/AAC.00779-08
identifier_str_mv FERRAZ, Marcela Lencine et al. Absence of CD4+ T lymphocytes, CD8+ T lymphocytes, or B lymphocytes has different effects on the efficacy of posaconazole and benznidazole in treatment of experimental acute Trypanosoma cruzi infection. Antimicrob Agents Chemother., v. 53, n. 1, p. 174-179, 2009. doi: 10.1128/AAC.00779-08.
0066-4804
10.1128/AAC.00779-08
url https://www.arca.fiocruz.br/handle/icict/58342
dc.language.iso.fl_str_mv eng
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dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv American Society for Microbiology
publisher.none.fl_str_mv American Society for Microbiology
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
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