Treatment with pCramoll alone and in combination with Fluconazole provides therapeutic benefits in C. gattii infected mice
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Outros Autores: | , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UFMG |
Texto Completo: | https://doi.org/10.3389/fcimb.2017.00211 http://hdl.handle.net/1843/56304 https://orcid.org/0000-0003-0381-9225 https://orcid.org/0000-0001-6918-1186 https://orcid.org/0000-0002-1013-0023 https://orcid.org/0000-0002-1108-5666 |
Resumo: | Cryptococcus gattii is one of the main causative agents of cryptococcosis in immunocompetent individuals. Treatment of the infection is based on the use of antimycotics, however, the toxicity of these drugs and the increase of drug-resistant strains have driven the search for more effective and less toxic therapies for cryptococcosis. pCramoll are isolectins purified from seeds of Cratylia mollis, a native forage plant from Brazil, which has become a versatile tool for biomedical application. We evaluated the effect of pCramoll alone and in combination with fluconazole for the treatment of mice infected with C. gatti. pCramoll alone or in combination with fluconazole increased the survival, reduced the morbidity and improved mice behavior i.e., neuropsychiatric state, motor behavior, autonomic function, muscle tone and strength and reflex/sensory function. These results were associated with (i) decreased pulmonary and cerebral fungal burden and (ii) increased inflammatory infiltrate and modulatory of IFNγ, IL-6, IL-10, and IL-17A cytokines in mice treated with pCramoll. Indeed, bone marrow-derived macrophages pulsed with pCramoll had increased ability to engulf C. gattii, with an enhanced production of reactive oxygen species and decrease of intracellular fungal proliferation. These findings point toward the use of pCramoll in combination with fluconazole as a viable, alternative therapy for cryptococcosis management. |
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2023-07-14T20:37:48Z2023-07-14T20:37:48Z20177https://doi.org/10.3389/fcimb.2017.002112235-2988http://hdl.handle.net/1843/56304https://orcid.org/0000-0003-0381-9225https://orcid.org/0000-0001-6918-1186https://orcid.org/0000-0002-1013-0023https://orcid.org/0000-0002-1108-5666Cryptococcus gattii is one of the main causative agents of cryptococcosis in immunocompetent individuals. Treatment of the infection is based on the use of antimycotics, however, the toxicity of these drugs and the increase of drug-resistant strains have driven the search for more effective and less toxic therapies for cryptococcosis. pCramoll are isolectins purified from seeds of Cratylia mollis, a native forage plant from Brazil, which has become a versatile tool for biomedical application. We evaluated the effect of pCramoll alone and in combination with fluconazole for the treatment of mice infected with C. gatti. pCramoll alone or in combination with fluconazole increased the survival, reduced the morbidity and improved mice behavior i.e., neuropsychiatric state, motor behavior, autonomic function, muscle tone and strength and reflex/sensory function. These results were associated with (i) decreased pulmonary and cerebral fungal burden and (ii) increased inflammatory infiltrate and modulatory of IFNγ, IL-6, IL-10, and IL-17A cytokines in mice treated with pCramoll. Indeed, bone marrow-derived macrophages pulsed with pCramoll had increased ability to engulf C. gattii, with an enhanced production of reactive oxygen species and decrease of intracellular fungal proliferation. These findings point toward the use of pCramoll in combination with fluconazole as a viable, alternative therapy for cryptococcosis management.Cryptococcus gattii é um dos principais agentes causadores de criptococose em indivíduos imunocompetentes. O tratamento da infecção é baseado no uso de antimicóticos, entretanto, a toxicidade dessas drogas e o aumento de cepas resistentes têm impulsionado a busca por terapias mais eficazes e menos tóxicas para a criptococose. pCramoll são isolectinas purificadas de sementes de Cratylia mollis, uma planta forrageira nativa do Brasil, que se tornou uma ferramenta versátil para aplicação biomédica. Avaliamos o efeito de pCramoll sozinho e em combinação com fluconazol para o tratamento de camundongos infectados com C. gatti. pCramoll sozinho ou em combinação com fluconazol aumentou a sobrevida, reduziu a morbidade e melhorou o comportamento dos camundongos, isto é, estado neuropsiquiátrico, comportamento motor, função autonômica, tônus e força muscular e função reflexa/sensorial. Esses resultados foram associados com (i) diminuição da carga fúngica pulmonar e cerebral e (ii) aumento do infiltrado inflamatório e citocinas moduladoras de IFNγ, IL-6, IL-10 e IL-17A em camundongos tratados com pCramoll. De fato, os macrófagos derivados da medula óssea pulsados com pCramoll aumentaram a capacidade de englobar C. gattii, com aumento da produção de espécies reativas de oxigênio e diminuição da proliferação fúngica intracelular. Esses achados apontam para o uso de pCramoll em combinação com fluconazol como uma terapia alternativa viável para o tratamento da criptococose.engUniversidade Federal de Minas GeraisUFMGBrasilICB - DEPARTAMENTO DE MICROBIOLOGIAICB - DEPARTAMENTO DE PATOLOGIAFrontiers in Cellular and Infection MicrobiologyCriptococoseImunomodulaçãoLectinasFabaceaeFluconazolCryptococcosisImmunomodulationLectinsCratylia mollis lectinFluconazoleSurvivalTreatment with pCramoll alone and in combination with Fluconazole provides therapeutic benefits in C. gattii infected miceO tratamento com pCramoll sozinho e em combinação com Fluconazol fornece benefícios terapêuticos em camundongos infectados por C. gattiiinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttps://www.frontiersin.org/articles/10.3389/fcimb.2017.00211/fullJannyson José Braz JandúMarliete Carvalho da CostaJulliana Ribeiro Alves SantosFernanda Miguel de AndradeThaís Furtado Ferreira MagalhãesMárcia Vanusa da SilvaMaria Carolina Accioly Brelaz de CastroLuana Cassandra Breitenbach Barroso CoelhoAline Gonçalves GomesTatiane Alves PaixãoDaniel de Assis SantosMaria Tereza Dos Santos Correiaapplication/pdfinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFMGinstname:Universidade Federal de Minas Gerais (UFMG)instacron:UFMGLICENSELicense.txtLicense.txttext/plain; charset=utf-82042https://repositorio.ufmg.br/bitstream/1843/56304/1/License.txtfa505098d172de0bc8864fc1287ffe22MD51ORIGINALTreatment with pcramoll alone and in combination with fluconazole provides therapeutic benefits in c. gattii infected mice.pdfTreatment with pcramoll alone and in combination with fluconazole provides therapeutic benefits in c. gattii infected mice.pdfapplication/pdf32523999https://repositorio.ufmg.br/bitstream/1843/56304/2/Treatment%20with%20pcramoll%20alone%20and%20in%20combination%20with%20fluconazole%20provides%20therapeutic%20benefits%20in%20c.%20gattii%20infected%20mice.pdf4117b0887c0ec5b5a602acc1a4017dccMD521843/563042023-07-14 17:37:48.878oai:repositorio.ufmg.br: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Repositório de PublicaçõesPUBhttps://repositorio.ufmg.br/oaiopendoar:2023-07-14T20:37:48Repositório Institucional da UFMG - Universidade Federal de Minas Gerais (UFMG)false |
dc.title.pt_BR.fl_str_mv |
Treatment with pCramoll alone and in combination with Fluconazole provides therapeutic benefits in C. gattii infected mice |
dc.title.alternative.pt_BR.fl_str_mv |
O tratamento com pCramoll sozinho e em combinação com Fluconazol fornece benefícios terapêuticos em camundongos infectados por C. gattii |
title |
Treatment with pCramoll alone and in combination with Fluconazole provides therapeutic benefits in C. gattii infected mice |
spellingShingle |
Treatment with pCramoll alone and in combination with Fluconazole provides therapeutic benefits in C. gattii infected mice Jannyson José Braz Jandú Cryptococcosis Immunomodulation Lectins Cratylia mollis lectin Fluconazole Survival Criptococose Imunomodulação Lectinas Fabaceae Fluconazol |
title_short |
Treatment with pCramoll alone and in combination with Fluconazole provides therapeutic benefits in C. gattii infected mice |
title_full |
Treatment with pCramoll alone and in combination with Fluconazole provides therapeutic benefits in C. gattii infected mice |
title_fullStr |
Treatment with pCramoll alone and in combination with Fluconazole provides therapeutic benefits in C. gattii infected mice |
title_full_unstemmed |
Treatment with pCramoll alone and in combination with Fluconazole provides therapeutic benefits in C. gattii infected mice |
title_sort |
Treatment with pCramoll alone and in combination with Fluconazole provides therapeutic benefits in C. gattii infected mice |
author |
Jannyson José Braz Jandú |
author_facet |
Jannyson José Braz Jandú Marliete Carvalho da Costa Julliana Ribeiro Alves Santos Fernanda Miguel de Andrade Thaís Furtado Ferreira Magalhães Márcia Vanusa da Silva Maria Carolina Accioly Brelaz de Castro Luana Cassandra Breitenbach Barroso Coelho Aline Gonçalves Gomes Tatiane Alves Paixão Daniel de Assis Santos Maria Tereza Dos Santos Correia |
author_role |
author |
author2 |
Marliete Carvalho da Costa Julliana Ribeiro Alves Santos Fernanda Miguel de Andrade Thaís Furtado Ferreira Magalhães Márcia Vanusa da Silva Maria Carolina Accioly Brelaz de Castro Luana Cassandra Breitenbach Barroso Coelho Aline Gonçalves Gomes Tatiane Alves Paixão Daniel de Assis Santos Maria Tereza Dos Santos Correia |
author2_role |
author author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Jannyson José Braz Jandú Marliete Carvalho da Costa Julliana Ribeiro Alves Santos Fernanda Miguel de Andrade Thaís Furtado Ferreira Magalhães Márcia Vanusa da Silva Maria Carolina Accioly Brelaz de Castro Luana Cassandra Breitenbach Barroso Coelho Aline Gonçalves Gomes Tatiane Alves Paixão Daniel de Assis Santos Maria Tereza Dos Santos Correia |
dc.subject.por.fl_str_mv |
Cryptococcosis Immunomodulation Lectins Cratylia mollis lectin Fluconazole Survival |
topic |
Cryptococcosis Immunomodulation Lectins Cratylia mollis lectin Fluconazole Survival Criptococose Imunomodulação Lectinas Fabaceae Fluconazol |
dc.subject.other.pt_BR.fl_str_mv |
Criptococose Imunomodulação Lectinas Fabaceae Fluconazol |
description |
Cryptococcus gattii is one of the main causative agents of cryptococcosis in immunocompetent individuals. Treatment of the infection is based on the use of antimycotics, however, the toxicity of these drugs and the increase of drug-resistant strains have driven the search for more effective and less toxic therapies for cryptococcosis. pCramoll are isolectins purified from seeds of Cratylia mollis, a native forage plant from Brazil, which has become a versatile tool for biomedical application. We evaluated the effect of pCramoll alone and in combination with fluconazole for the treatment of mice infected with C. gatti. pCramoll alone or in combination with fluconazole increased the survival, reduced the morbidity and improved mice behavior i.e., neuropsychiatric state, motor behavior, autonomic function, muscle tone and strength and reflex/sensory function. These results were associated with (i) decreased pulmonary and cerebral fungal burden and (ii) increased inflammatory infiltrate and modulatory of IFNγ, IL-6, IL-10, and IL-17A cytokines in mice treated with pCramoll. Indeed, bone marrow-derived macrophages pulsed with pCramoll had increased ability to engulf C. gattii, with an enhanced production of reactive oxygen species and decrease of intracellular fungal proliferation. These findings point toward the use of pCramoll in combination with fluconazole as a viable, alternative therapy for cryptococcosis management. |
publishDate |
2017 |
dc.date.issued.fl_str_mv |
2017 |
dc.date.accessioned.fl_str_mv |
2023-07-14T20:37:48Z |
dc.date.available.fl_str_mv |
2023-07-14T20:37:48Z |
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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article |
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publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/1843/56304 |
dc.identifier.doi.pt_BR.fl_str_mv |
https://doi.org/10.3389/fcimb.2017.00211 |
dc.identifier.issn.pt_BR.fl_str_mv |
2235-2988 |
dc.identifier.orcid.pt_BR.fl_str_mv |
https://orcid.org/0000-0003-0381-9225 https://orcid.org/0000-0001-6918-1186 https://orcid.org/0000-0002-1013-0023 https://orcid.org/0000-0002-1108-5666 |
url |
https://doi.org/10.3389/fcimb.2017.00211 http://hdl.handle.net/1843/56304 https://orcid.org/0000-0003-0381-9225 https://orcid.org/0000-0001-6918-1186 https://orcid.org/0000-0002-1013-0023 https://orcid.org/0000-0002-1108-5666 |
identifier_str_mv |
2235-2988 |
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eng |
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eng |
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Frontiers in Cellular and Infection Microbiology |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
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Universidade Federal de Minas Gerais |
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UFMG |
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Brasil |
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ICB - DEPARTAMENTO DE MICROBIOLOGIA ICB - DEPARTAMENTO DE PATOLOGIA |
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Universidade Federal de Minas Gerais |
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