Estudo da maturação de células dendríticas em indivíduos portadores de hanseníase

Detalhes bibliográficos
Autor(a) principal: Braga, André Flores [UNESP]
Data de Publicação: 2014
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Repositório Institucional da UNESP
Texto Completo: http://hdl.handle.net/11449/113892
Resumo: Leprosy is caused by Mycobacterium leprae and characterized by distinct clinical manifestations that reflect the immune response of the host. Dendritic cells (DCs) play a crucial role in immunity inducing the development of adaptive immune response, however the interaction of DCs with M. leprae is poorly understood. This study aims to contribute to the understanding of the generation of specific immune response in leprosy patients focusing on the role of DCs against the M. leprae. DCs were differentiated in vitro from monocytes of lepromatous and tuberculoid patients, stimulated with sonicated antigen of M. leprae and analyzed for the expression of differentiation and maturation markers. The expression of mRNA to cytokines and receptors was assessed by qPCR. In parallel, monocytes from healthy controls were preincubated with the sonicated antigen of M. leprae, differentiated into DCs and evaluated in respect to the expression of surface markers. Differentiation of monocytes into DCs was similar between patients and healthy controls. After stimulation with sonicated antigen of M. leprae DCs from leprosy patients and healthy controls showed increased expression of CD40, CD80, CD86 and HLA-DR but this stimulation seems to be insufficient for complete activation of DCs since it was not observed an increase in the level of CD83. The analysis of gene expression also showed partial stimulation of DCs by M. leprae. The pre-incubation of monocytes with sonicated antigen of M. leprae resulted in impairment in the differentiation into DCs and maturation. Altogether our results suggest that the sonicated antigen of M. leprae impaired differentiation of monocytes into DCs and triggered an incomplete activation of DCs both in patients and healthy controls that may contribute among the mechanisms of escape used by M. leprae
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spelling Estudo da maturação de células dendríticas em indivíduos portadores de hanseníaseHanseniaseMycobacterium lepraeAntígenos bacterianosCélulas dendríticasResposta imuneExpressão gênicaAntigenosLeprosy is caused by Mycobacterium leprae and characterized by distinct clinical manifestations that reflect the immune response of the host. Dendritic cells (DCs) play a crucial role in immunity inducing the development of adaptive immune response, however the interaction of DCs with M. leprae is poorly understood. This study aims to contribute to the understanding of the generation of specific immune response in leprosy patients focusing on the role of DCs against the M. leprae. DCs were differentiated in vitro from monocytes of lepromatous and tuberculoid patients, stimulated with sonicated antigen of M. leprae and analyzed for the expression of differentiation and maturation markers. The expression of mRNA to cytokines and receptors was assessed by qPCR. In parallel, monocytes from healthy controls were preincubated with the sonicated antigen of M. leprae, differentiated into DCs and evaluated in respect to the expression of surface markers. Differentiation of monocytes into DCs was similar between patients and healthy controls. After stimulation with sonicated antigen of M. leprae DCs from leprosy patients and healthy controls showed increased expression of CD40, CD80, CD86 and HLA-DR but this stimulation seems to be insufficient for complete activation of DCs since it was not observed an increase in the level of CD83. The analysis of gene expression also showed partial stimulation of DCs by M. leprae. The pre-incubation of monocytes with sonicated antigen of M. leprae resulted in impairment in the differentiation into DCs and maturation. Altogether our results suggest that the sonicated antigen of M. leprae impaired differentiation of monocytes into DCs and triggered an incomplete activation of DCs both in patients and healthy controls that may contribute among the mechanisms of escape used by M. lepraeA hanseníase, causada pelo Mycobacterium leprae, apresenta diferentes quadros clínicos que refletem o perfil de resposta imunológica do hospedeiro. As células dendríticas (DCs) possuem um papel crucial na imunidade por induzirem o desenvolvimento da resposta imune adaptativa, porém a interação do M. leprae com estas células ainda é pouco entendida. Neste estudo buscamos contribuir para o entendimento da geração da resposta imune específica na hanseníase tendo como foco o papel das DCs frente ao M. leprae. DCs foram diferenciadas in vitro a partir de monócitos de pacientes tuberculóides e virchowianos, estimuladas com antígeno sonicado do M. leprae e analisadas quanto à expressão de marcadores de diferenciação e maturação. A expressão de genes de citocinas e receptores foi avaliada por qPCR. Paralelamente, monócitos de indivíduos saudáveis foram pré-incubados com o antígeno sonicado do bacilo e submetidos à diferenciação em DCs e à avaliação dos marcadores de superfície. A diferenciação de monócitos em DCs foi similar entre pacientes e controles saudáveis. A estimulação com o antígeno sonicado do M. leprae levou ao aumento na expressão de CD40, CD80, CD86 e HLA-DR tanto nos pacientes hansenianos como em indivíduos saudáveis. Entretato, este estímulo parece ser insuficiente para a completa ativação das DCs uma vez que não resultou em aumento significativo nos níveis de CD83. A análise da expressão gênica também demonstrou estimulação parcial das DCs pelo M. leprae. A pré-incubação de monócitos com o antígeno sonicado do bacilo comprometeu o processo de diferenciação em DCs e a maturação destas. Em conjunto, nossos resultados sugerem que o antígeno sonicado do M. leprae prejudicou a diferenciação de monócitos em DCs e desencadeou uma ativação incompleta das DCs tanto em pacientes quanto em controles saudáveis o que pode contribuir para os mecanismos de escape do baciloFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)FAPESP: 09/01436-1Universidade Estadual Paulista (Unesp)Souza, Vânia Nieto Brito de [UNESP]Latini, Ana Carla Pereira [UNESP]Universidade Estadual Paulista (Unesp)Braga, André Flores [UNESP]2015-01-26T13:21:21Z2015-01-26T13:21:21Z2014-07-29info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesis54 f.application/pdfBRAGA, André Flores. Estudo da maturação de células dendríticas em indivíduos portadores de hanseníase. 2014. 54 f. Dissertação (mestrado) - Universidade Estadual Paulista Júlio de Mesquita Filho, Faculdade de Medicina de Botucatu, 2014.http://hdl.handle.net/11449/113892000795829000795829.pdf33004064065P4Alephreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPporinfo:eu-repo/semantics/openAccess2024-01-10T06:29:39Zoai:repositorio.unesp.br:11449/113892Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-01-10T06:29:39Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv Estudo da maturação de células dendríticas em indivíduos portadores de hanseníase
title Estudo da maturação de células dendríticas em indivíduos portadores de hanseníase
spellingShingle Estudo da maturação de células dendríticas em indivíduos portadores de hanseníase
Braga, André Flores [UNESP]
Hanseniase
Mycobacterium leprae
Antígenos bacterianos
Células dendríticas
Resposta imune
Expressão gênica
Antigenos
title_short Estudo da maturação de células dendríticas em indivíduos portadores de hanseníase
title_full Estudo da maturação de células dendríticas em indivíduos portadores de hanseníase
title_fullStr Estudo da maturação de células dendríticas em indivíduos portadores de hanseníase
title_full_unstemmed Estudo da maturação de células dendríticas em indivíduos portadores de hanseníase
title_sort Estudo da maturação de células dendríticas em indivíduos portadores de hanseníase
author Braga, André Flores [UNESP]
author_facet Braga, André Flores [UNESP]
author_role author
dc.contributor.none.fl_str_mv Souza, Vânia Nieto Brito de [UNESP]
Latini, Ana Carla Pereira [UNESP]
Universidade Estadual Paulista (Unesp)
dc.contributor.author.fl_str_mv Braga, André Flores [UNESP]
dc.subject.por.fl_str_mv Hanseniase
Mycobacterium leprae
Antígenos bacterianos
Células dendríticas
Resposta imune
Expressão gênica
Antigenos
topic Hanseniase
Mycobacterium leprae
Antígenos bacterianos
Células dendríticas
Resposta imune
Expressão gênica
Antigenos
description Leprosy is caused by Mycobacterium leprae and characterized by distinct clinical manifestations that reflect the immune response of the host. Dendritic cells (DCs) play a crucial role in immunity inducing the development of adaptive immune response, however the interaction of DCs with M. leprae is poorly understood. This study aims to contribute to the understanding of the generation of specific immune response in leprosy patients focusing on the role of DCs against the M. leprae. DCs were differentiated in vitro from monocytes of lepromatous and tuberculoid patients, stimulated with sonicated antigen of M. leprae and analyzed for the expression of differentiation and maturation markers. The expression of mRNA to cytokines and receptors was assessed by qPCR. In parallel, monocytes from healthy controls were preincubated with the sonicated antigen of M. leprae, differentiated into DCs and evaluated in respect to the expression of surface markers. Differentiation of monocytes into DCs was similar between patients and healthy controls. After stimulation with sonicated antigen of M. leprae DCs from leprosy patients and healthy controls showed increased expression of CD40, CD80, CD86 and HLA-DR but this stimulation seems to be insufficient for complete activation of DCs since it was not observed an increase in the level of CD83. The analysis of gene expression also showed partial stimulation of DCs by M. leprae. The pre-incubation of monocytes with sonicated antigen of M. leprae resulted in impairment in the differentiation into DCs and maturation. Altogether our results suggest that the sonicated antigen of M. leprae impaired differentiation of monocytes into DCs and triggered an incomplete activation of DCs both in patients and healthy controls that may contribute among the mechanisms of escape used by M. leprae
publishDate 2014
dc.date.none.fl_str_mv 2014-07-29
2015-01-26T13:21:21Z
2015-01-26T13:21:21Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
format masterThesis
status_str publishedVersion
dc.identifier.uri.fl_str_mv BRAGA, André Flores. Estudo da maturação de células dendríticas em indivíduos portadores de hanseníase. 2014. 54 f. Dissertação (mestrado) - Universidade Estadual Paulista Júlio de Mesquita Filho, Faculdade de Medicina de Botucatu, 2014.
http://hdl.handle.net/11449/113892
000795829
000795829.pdf
33004064065P4
identifier_str_mv BRAGA, André Flores. Estudo da maturação de células dendríticas em indivíduos portadores de hanseníase. 2014. 54 f. Dissertação (mestrado) - Universidade Estadual Paulista Júlio de Mesquita Filho, Faculdade de Medicina de Botucatu, 2014.
000795829
000795829.pdf
33004064065P4
url http://hdl.handle.net/11449/113892
dc.language.iso.fl_str_mv por
language por
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 54 f.
application/pdf
dc.publisher.none.fl_str_mv Universidade Estadual Paulista (Unesp)
publisher.none.fl_str_mv Universidade Estadual Paulista (Unesp)
dc.source.none.fl_str_mv Aleph
reponame:Repositório Institucional da UNESP
instname:Universidade Estadual Paulista (UNESP)
instacron:UNESP
instname_str Universidade Estadual Paulista (UNESP)
instacron_str UNESP
institution UNESP
reponame_str Repositório Institucional da UNESP
collection Repositório Institucional da UNESP
repository.name.fl_str_mv Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)
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