AvaliaÃÃo do mecanismo de modulaÃÃo da resposta imunolÃgica à Leishmaniose visceral chagasi in vitro em indivÃduos baixos produtores de INF-Y

Detalhes bibliográficos
Autor(a) principal: MÃrcia Sindeaux Frutuoso
Data de Publicação: 2009
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Biblioteca Digital de Teses e Dissertações da UFC
Texto Completo: http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=8664
Resumo: Introduction: Visceral leishmaniasis is a serious public health problem in several parts of the developing world. In leishmaniasis, protection and healing correlate with the development of Th1 immune response, and IFN-γ is considered a key molecule in this response. In contrast, the Th2 response results in disease progression. It is noteworthy that after contact with Leishmania the production of IFN-γ differs between healthy individuals. Some of them are high IFN-γ producer (HIFN-γP), while others respond with low IFN-γ producer (LIFN-γP). This has been observed in the in vitro response to several species of Leishmania, as well as in the early phase of the disease in patients with leishmaniasis. The activation of T lymphocytes can be modulated by immunomodulatory receptors present on the surface of lymphocytes and antigen presenting cells (APCs). Signaling lymphocytic activation molecule (SLAM, CD150) is a transmembrane protein that promotes Th2 differentiation. Evidences support the involvement of this molecule in the immune response against parasites. Objective: To evaluate the role of SLAM signaling pathway in the modulation of immune response of peripheral blood mononuclear cells (PBMC) from individuals low IFN-γ producers (LP) against Leishmania chagasi. Methodology: Healthy individualsâ PBMC were stimulated in vitro with L. chagasi and monoclonal anti-SLAM (α-SLAM), in the presence or not of inflammatory cytokines (rIFN-γ or rIL-12). The supernatants of the cultures were analyzed by ELISA for the determination of IFN-γ and interleukin 10 (IL-10) concentrations. Results: Upon stimulation of PBMC with L. chagasi, the blocking of the SLAM signaling pathway with α-SLAM did not affect the synthesis of IFN-γ and IL-10, regardless of treatment with rIL-12. However, after rIFN-γ treatment of antigen stimulated cells it occurred a download of IL-10 synthesis and upload IFN-γ secretion, regardless of the blockade of SLAM signaling pathway. Conclusions: The blocking of SLAM signaling pathway with α-SLAM at the concentration of 10μg/mL does not interfere significantly in the IFN-γ and IL-10 production of PBMC from individuals LP stimulated with Leishmania chagasi promastigotes. Treatment of PBMC with rIFN-γ is able to induce a reduction of IL-10 and an increment of IFN-γ in the supernates cultures, whereas treatment with rIL-12 enhanced IFN-γ production, but does not interfered with IL-10. It is necessary to make further studies to better understand the role of the SLAM signaling pathway in the immune response of LP against Leishmania chagasi.
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spelling info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisAvaliaÃÃo do mecanismo de modulaÃÃo da resposta imunolÃgica à Leishmaniose visceral chagasi in vitro em indivÃduos baixos produtores de INF-YMODULATION OF IN VITRO IMMUNE RESPONSE TO LOW IFN-γ RESPONSRES AGAINST LEISHMANIA CHAGASI 2009-09-26Margarida Maria de Lima Pompeu11779420382Diana CÃlia Sousa Nunes-Pinheiro15563278387http://lattes.cnpq.br/3376562859305916Max Victor Carioca Freitas67953662353http://lattes.cnpq.br/2609171032311880Ãrika Freitas Mota54454956391http://lattes.cnpq.br/596416512742963095042334300http://lattes.cnpq.br/4140385575850782MÃrcia Sindeaux FrutuosoUniversidade Federal do CearÃPrograma de PÃs-GraduaÃÃo em PatologiaUFCBRLeishmania chagasi SLAM IFN-&#947 IL-10SLAMIFN-γIL-10ANATOMIA PATOLOGICA E PATOLOGIA CLINICAIntroduction: Visceral leishmaniasis is a serious public health problem in several parts of the developing world. In leishmaniasis, protection and healing correlate with the development of Th1 immune response, and IFN-γ is considered a key molecule in this response. In contrast, the Th2 response results in disease progression. It is noteworthy that after contact with Leishmania the production of IFN-γ differs between healthy individuals. Some of them are high IFN-γ producer (HIFN-γP), while others respond with low IFN-γ producer (LIFN-γP). This has been observed in the in vitro response to several species of Leishmania, as well as in the early phase of the disease in patients with leishmaniasis. The activation of T lymphocytes can be modulated by immunomodulatory receptors present on the surface of lymphocytes and antigen presenting cells (APCs). Signaling lymphocytic activation molecule (SLAM, CD150) is a transmembrane protein that promotes Th2 differentiation. Evidences support the involvement of this molecule in the immune response against parasites. Objective: To evaluate the role of SLAM signaling pathway in the modulation of immune response of peripheral blood mononuclear cells (PBMC) from individuals low IFN-γ producers (LP) against Leishmania chagasi. Methodology: Healthy individualsâ PBMC were stimulated in vitro with L. chagasi and monoclonal anti-SLAM (α-SLAM), in the presence or not of inflammatory cytokines (rIFN-γ or rIL-12). The supernatants of the cultures were analyzed by ELISA for the determination of IFN-γ and interleukin 10 (IL-10) concentrations. Results: Upon stimulation of PBMC with L. chagasi, the blocking of the SLAM signaling pathway with α-SLAM did not affect the synthesis of IFN-γ and IL-10, regardless of treatment with rIL-12. However, after rIFN-γ treatment of antigen stimulated cells it occurred a download of IL-10 synthesis and upload IFN-γ secretion, regardless of the blockade of SLAM signaling pathway. Conclusions: The blocking of SLAM signaling pathway with α-SLAM at the concentration of 10μg/mL does not interfere significantly in the IFN-γ and IL-10 production of PBMC from individuals LP stimulated with Leishmania chagasi promastigotes. Treatment of PBMC with rIFN-γ is able to induce a reduction of IL-10 and an increment of IFN-γ in the supernates cultures, whereas treatment with rIL-12 enhanced IFN-γ production, but does not interfered with IL-10. It is necessary to make further studies to better understand the role of the SLAM signaling pathway in the immune response of LP against Leishmania chagasi. IntroduÃÃo: Nas leishmanioses, proteÃÃo e cura se correlacionam com o desenvolvimento de resposta imune tipo Th1, e IFN-γ à considerada uma molÃcula chave nesta resposta. Ao contrÃrio, a resposta Th2, resulta na progressÃo da doenÃa. Vale ressaltar que a produÃÃo de IFN-γ, apÃs o contato com a Leishmania, difere entre indivÃduos sadios, alguns apresentam alta produÃÃo de IFN-γ (AP), enquanto outros respondem com baixa produÃÃo (BP). Isto tem sido observado com diversas espÃcies de Leishmania, assim como na infecÃÃo natural, na fase inicial da doenÃa. A ativaÃÃo do linfÃcito T pode ser modulada por coestimuladores, presentes na superfÃcie de linfÃcitos e nas APCs, a exemplo da molÃcula sinalizadora na ativaÃÃo de linfÃcitos T (SLAM). EvidÃncias apontam para o envolvimento dessas molÃculas na regulaÃÃo da resposta imunolÃgica. Objetivo: Avaliar o papel da via de sinalizaÃÃo de SLAM na modulaÃÃo da resposta imune em cÃlulas mononucleares de sangue perifÃrico (CMSP) de indivÃduos BP, frente à estimulaÃÃo in vitro por Leishmania chagasi. Metodologia: CMSP de indivÃduos sadios BP foram estimuladas in vitro com L. chagasi na ausÃncia ou na presenÃa do anticorpo monoclonal anti-SLAM (α-SLAM), com ou sem tratamento por citocinas proinflamatÃrias (rIFN-γ ou rIL-12). Os sobrenadantes das culturas foram analisados por ELISA para IFN-γ e interleucina (IL)-10. Resultados: Sob estimulaÃÃo de L. chagasi, o bloqueio da via SLAM nÃo modificou a sÃntese de IFN-γ e IL-10, independente do tratamento com rIL-12. No entanto, o tratamento com rIFN-γ reduziu a sÃntese de IL-10 e elevou a secreÃÃo de IFN-γ endÃgeno, independente do bloqueio da via SLAM. ConclusÃes: O bloqueio da via SLAM, com adiÃÃo de α-SLAM (10Âg/mL), nÃo interfere significativamente na produÃÃo de IFN-γ e IL-10. O tratamento das CMSP com rIFN-γ à capaz de induzir a reduÃÃo da produÃÃo de IL-10 e o aumento de IFN-γ de forma significativa, enquanto que o tratamento com rIL-12 aumenta a produÃÃo de IFN-γ, mas nÃo interfere na produÃÃo de IL-10 dos indivÃduos baixos produtores. Faz-se necessÃrio ampliar o estudo da aÃÃo imunomoduladora da SLAM frente à Leishmania chagasi, para um melhor entendimento do papel desta via de sinalizaÃÃo na resposta imunolÃgica dos BP. CoordenaÃÃo de AperfeiÃoamento de NÃvel Superiorhttp://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=8664application/pdfinfo:eu-repo/semantics/openAccessporreponame:Biblioteca Digital de Teses e Dissertações da UFCinstname:Universidade Federal do Cearáinstacron:UFC2019-01-21T11:21:48Zmail@mail.com -
dc.title.pt.fl_str_mv AvaliaÃÃo do mecanismo de modulaÃÃo da resposta imunolÃgica à Leishmaniose visceral chagasi in vitro em indivÃduos baixos produtores de INF-Y
dc.title.alternative..fl_str_mv MODULATION OF IN VITRO IMMUNE RESPONSE TO LOW IFN-γ RESPONSRES AGAINST LEISHMANIA CHAGASI
title AvaliaÃÃo do mecanismo de modulaÃÃo da resposta imunolÃgica à Leishmaniose visceral chagasi in vitro em indivÃduos baixos produtores de INF-Y
spellingShingle AvaliaÃÃo do mecanismo de modulaÃÃo da resposta imunolÃgica à Leishmaniose visceral chagasi in vitro em indivÃduos baixos produtores de INF-Y
MÃrcia Sindeaux Frutuoso
SLAM
IFN-γ
IL-10
ANATOMIA PATOLOGICA E PATOLOGIA CLINICA
title_short AvaliaÃÃo do mecanismo de modulaÃÃo da resposta imunolÃgica à Leishmaniose visceral chagasi in vitro em indivÃduos baixos produtores de INF-Y
title_full AvaliaÃÃo do mecanismo de modulaÃÃo da resposta imunolÃgica à Leishmaniose visceral chagasi in vitro em indivÃduos baixos produtores de INF-Y
title_fullStr AvaliaÃÃo do mecanismo de modulaÃÃo da resposta imunolÃgica à Leishmaniose visceral chagasi in vitro em indivÃduos baixos produtores de INF-Y
title_full_unstemmed AvaliaÃÃo do mecanismo de modulaÃÃo da resposta imunolÃgica à Leishmaniose visceral chagasi in vitro em indivÃduos baixos produtores de INF-Y
title_sort AvaliaÃÃo do mecanismo de modulaÃÃo da resposta imunolÃgica à Leishmaniose visceral chagasi in vitro em indivÃduos baixos produtores de INF-Y
author MÃrcia Sindeaux Frutuoso
author_facet MÃrcia Sindeaux Frutuoso
author_role author
dc.contributor.advisor1.fl_str_mv Margarida Maria de Lima Pompeu
dc.contributor.advisor1ID.fl_str_mv 11779420382
dc.contributor.referee1.fl_str_mv Diana CÃlia Sousa Nunes-Pinheiro
dc.contributor.referee1ID.fl_str_mv 15563278387
dc.contributor.referee1Lattes.fl_str_mv http://lattes.cnpq.br/3376562859305916
dc.contributor.referee2.fl_str_mv Max Victor Carioca Freitas
dc.contributor.referee2ID.fl_str_mv 67953662353
dc.contributor.referee2Lattes.fl_str_mv http://lattes.cnpq.br/2609171032311880
dc.contributor.referee3.fl_str_mv Ãrika Freitas Mota
dc.contributor.referee3ID.fl_str_mv 54454956391
dc.contributor.referee3Lattes.fl_str_mv http://lattes.cnpq.br/5964165127429630
dc.contributor.authorID.fl_str_mv 95042334300
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/4140385575850782
dc.contributor.author.fl_str_mv MÃrcia Sindeaux Frutuoso
contributor_str_mv Margarida Maria de Lima Pompeu
Diana CÃlia Sousa Nunes-Pinheiro
Max Victor Carioca Freitas
Ãrika Freitas Mota
dc.subject.por.fl_str_mv SLAM
IFN-γ
IL-10
topic SLAM
IFN-γ
IL-10
ANATOMIA PATOLOGICA E PATOLOGIA CLINICA
dc.subject.cnpq.fl_str_mv ANATOMIA PATOLOGICA E PATOLOGIA CLINICA
dc.description.sponsorship.fl_txt_mv CoordenaÃÃo de AperfeiÃoamento de NÃvel Superior
dc.description.abstract..fl_txt_mv Introduction: Visceral leishmaniasis is a serious public health problem in several parts of the developing world. In leishmaniasis, protection and healing correlate with the development of Th1 immune response, and IFN-γ is considered a key molecule in this response. In contrast, the Th2 response results in disease progression. It is noteworthy that after contact with Leishmania the production of IFN-γ differs between healthy individuals. Some of them are high IFN-γ producer (HIFN-γP), while others respond with low IFN-γ producer (LIFN-γP). This has been observed in the in vitro response to several species of Leishmania, as well as in the early phase of the disease in patients with leishmaniasis. The activation of T lymphocytes can be modulated by immunomodulatory receptors present on the surface of lymphocytes and antigen presenting cells (APCs). Signaling lymphocytic activation molecule (SLAM, CD150) is a transmembrane protein that promotes Th2 differentiation. Evidences support the involvement of this molecule in the immune response against parasites. Objective: To evaluate the role of SLAM signaling pathway in the modulation of immune response of peripheral blood mononuclear cells (PBMC) from individuals low IFN-γ producers (LP) against Leishmania chagasi. Methodology: Healthy individualsâ PBMC were stimulated in vitro with L. chagasi and monoclonal anti-SLAM (α-SLAM), in the presence or not of inflammatory cytokines (rIFN-γ or rIL-12). The supernatants of the cultures were analyzed by ELISA for the determination of IFN-γ and interleukin 10 (IL-10) concentrations. Results: Upon stimulation of PBMC with L. chagasi, the blocking of the SLAM signaling pathway with α-SLAM did not affect the synthesis of IFN-γ and IL-10, regardless of treatment with rIL-12. However, after rIFN-γ treatment of antigen stimulated cells it occurred a download of IL-10 synthesis and upload IFN-γ secretion, regardless of the blockade of SLAM signaling pathway. Conclusions: The blocking of SLAM signaling pathway with α-SLAM at the concentration of 10μg/mL does not interfere significantly in the IFN-γ and IL-10 production of PBMC from individuals LP stimulated with Leishmania chagasi promastigotes. Treatment of PBMC with rIFN-γ is able to induce a reduction of IL-10 and an increment of IFN-γ in the supernates cultures, whereas treatment with rIL-12 enhanced IFN-γ production, but does not interfered with IL-10. It is necessary to make further studies to better understand the role of the SLAM signaling pathway in the immune response of LP against Leishmania chagasi.
dc.description.abstract.por.fl_txt_mv IntroduÃÃo: Nas leishmanioses, proteÃÃo e cura se correlacionam com o desenvolvimento de resposta imune tipo Th1, e IFN-γ à considerada uma molÃcula chave nesta resposta. Ao contrÃrio, a resposta Th2, resulta na progressÃo da doenÃa. Vale ressaltar que a produÃÃo de IFN-γ, apÃs o contato com a Leishmania, difere entre indivÃduos sadios, alguns apresentam alta produÃÃo de IFN-γ (AP), enquanto outros respondem com baixa produÃÃo (BP). Isto tem sido observado com diversas espÃcies de Leishmania, assim como na infecÃÃo natural, na fase inicial da doenÃa. A ativaÃÃo do linfÃcito T pode ser modulada por coestimuladores, presentes na superfÃcie de linfÃcitos e nas APCs, a exemplo da molÃcula sinalizadora na ativaÃÃo de linfÃcitos T (SLAM). EvidÃncias apontam para o envolvimento dessas molÃculas na regulaÃÃo da resposta imunolÃgica. Objetivo: Avaliar o papel da via de sinalizaÃÃo de SLAM na modulaÃÃo da resposta imune em cÃlulas mononucleares de sangue perifÃrico (CMSP) de indivÃduos BP, frente à estimulaÃÃo in vitro por Leishmania chagasi. Metodologia: CMSP de indivÃduos sadios BP foram estimuladas in vitro com L. chagasi na ausÃncia ou na presenÃa do anticorpo monoclonal anti-SLAM (α-SLAM), com ou sem tratamento por citocinas proinflamatÃrias (rIFN-γ ou rIL-12). Os sobrenadantes das culturas foram analisados por ELISA para IFN-γ e interleucina (IL)-10. Resultados: Sob estimulaÃÃo de L. chagasi, o bloqueio da via SLAM nÃo modificou a sÃntese de IFN-γ e IL-10, independente do tratamento com rIL-12. No entanto, o tratamento com rIFN-γ reduziu a sÃntese de IL-10 e elevou a secreÃÃo de IFN-γ endÃgeno, independente do bloqueio da via SLAM. ConclusÃes: O bloqueio da via SLAM, com adiÃÃo de α-SLAM (10Âg/mL), nÃo interfere significativamente na produÃÃo de IFN-γ e IL-10. O tratamento das CMSP com rIFN-γ à capaz de induzir a reduÃÃo da produÃÃo de IL-10 e o aumento de IFN-γ de forma significativa, enquanto que o tratamento com rIL-12 aumenta a produÃÃo de IFN-γ, mas nÃo interfere na produÃÃo de IL-10 dos indivÃduos baixos produtores. Faz-se necessÃrio ampliar o estudo da aÃÃo imunomoduladora da SLAM frente à Leishmania chagasi, para um melhor entendimento do papel desta via de sinalizaÃÃo na resposta imunolÃgica dos BP.
description Introduction: Visceral leishmaniasis is a serious public health problem in several parts of the developing world. In leishmaniasis, protection and healing correlate with the development of Th1 immune response, and IFN-γ is considered a key molecule in this response. In contrast, the Th2 response results in disease progression. It is noteworthy that after contact with Leishmania the production of IFN-γ differs between healthy individuals. Some of them are high IFN-γ producer (HIFN-γP), while others respond with low IFN-γ producer (LIFN-γP). This has been observed in the in vitro response to several species of Leishmania, as well as in the early phase of the disease in patients with leishmaniasis. The activation of T lymphocytes can be modulated by immunomodulatory receptors present on the surface of lymphocytes and antigen presenting cells (APCs). Signaling lymphocytic activation molecule (SLAM, CD150) is a transmembrane protein that promotes Th2 differentiation. Evidences support the involvement of this molecule in the immune response against parasites. Objective: To evaluate the role of SLAM signaling pathway in the modulation of immune response of peripheral blood mononuclear cells (PBMC) from individuals low IFN-γ producers (LP) against Leishmania chagasi. Methodology: Healthy individualsâ PBMC were stimulated in vitro with L. chagasi and monoclonal anti-SLAM (α-SLAM), in the presence or not of inflammatory cytokines (rIFN-γ or rIL-12). The supernatants of the cultures were analyzed by ELISA for the determination of IFN-γ and interleukin 10 (IL-10) concentrations. Results: Upon stimulation of PBMC with L. chagasi, the blocking of the SLAM signaling pathway with α-SLAM did not affect the synthesis of IFN-γ and IL-10, regardless of treatment with rIL-12. However, after rIFN-γ treatment of antigen stimulated cells it occurred a download of IL-10 synthesis and upload IFN-γ secretion, regardless of the blockade of SLAM signaling pathway. Conclusions: The blocking of SLAM signaling pathway with α-SLAM at the concentration of 10μg/mL does not interfere significantly in the IFN-γ and IL-10 production of PBMC from individuals LP stimulated with Leishmania chagasi promastigotes. Treatment of PBMC with rIFN-γ is able to induce a reduction of IL-10 and an increment of IFN-γ in the supernates cultures, whereas treatment with rIL-12 enhanced IFN-γ production, but does not interfered with IL-10. It is necessary to make further studies to better understand the role of the SLAM signaling pathway in the immune response of LP against Leishmania chagasi.
publishDate 2009
dc.date.issued.fl_str_mv 2009-09-26
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
status_str publishedVersion
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dc.publisher.none.fl_str_mv Universidade Federal do CearÃ
dc.publisher.program.fl_str_mv Programa de PÃs-GraduaÃÃo em Patologia
dc.publisher.initials.fl_str_mv UFC
dc.publisher.country.fl_str_mv BR
publisher.none.fl_str_mv Universidade Federal do CearÃ
dc.source.none.fl_str_mv reponame:Biblioteca Digital de Teses e Dissertações da UFC
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instname_str Universidade Federal do Ceará
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