Avaliação do papel das células B na hanseníase experimental
Autor(a) principal: | |
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Data de Publicação: | 2018 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Biblioteca Digital de Teses e Dissertações da USC |
Texto Completo: | http://tede2.usc.br:8080/jspui/handle/tede/402 |
Resumo: | Leprosy is a chronic infectious disease that mainly affects skin and peripheral nervous system, whose etiologic agent is the bacillus Mycobacterium leprae. Based on the clinical and histopathological characteristics, leprosy can be classified into two polar forms (tuberculoid and lepromatous), three intermediate or borderline forms (borderline-tuberculoid, borderline- borderline and borderline- lepromatous) and two reactional events (Type I and II). This broad spectrum of clinical forms is directly related to cellular immune response, with the influence of Th1, Th2, Th17 and regulatory T cells. Recently, B cells have also been described as important immunoregulatory elements, since they can produce different classes of cytokines and currently subdivided into effector B cells and regulatory B cells. Preliminary results from our group demonstrated that BKO knockout mice exhibit significantly larger bacillary plantar cushions than wild animals (WT), demonstrating the importance of such cells in experimental leprosy. The present study evaluated the expression of cytokines related to the immunopathology of leprosy (IFN-gamma, TNF-alpha, IL-4, IL-17, TGF -beta and IL-10) in the plantar cushions and lymph nodes of the BKO and WT mice. Additionally, to characterize the inflammatory infiltrate, the subpopulations of macrophages M1 and M2 present in the plantar cushions of both groups were phenotyped using the immunohistochemical technique. The results obtained demonstrated that expression of IL-4, IL-10 and TGF-beta cytokines was significantly higher in the BKO plantar cushions when compared to the WT group, but there was no difference in IFN-gamma, TNF-alpha and IL-17. In addition, in the lymph nodes, only IL-17 expression was significantly higher in the WT group. As for the inflammatory infiltrate, the number of M1 macrophages was significantly lower in the BKO group when compared to the WT group, whereas the number of M2 macrophages was significantly higher in the BKO and WT groups when compared to the M1 macrophages. The results obtained in this study demonstrated that the absence of B lymphocytes contribute to the persistence and multiplication of the bacillus, probably due to the increased expression of the IL-4, IL-10 and TGF-beta cytokines, as well as a decrease in the number of M1 macrophages in the inflammatory site. |
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Trombone-Garlet, Ana Paula Favaro24569954-5http://lattes.cnpq.br/8152853020428952Rosa, Patrícia Sammarco063.367.868-62http://lattes.cnpq.br/887015956486042525.697.532-2191.426.898-99http://lattes.cnpq.br/5983938584153951Marques, Heloisa2018-05-02T23:36:00Z2018-04-10MARQUES, Heloisa. Avaliação do papel das células B na hanseníase experimental. 2018. 76 f. Tese (Doutorado em Biologia Oral) - Universidade do Sagrado Coração, Bauru, 2018.http://tede2.usc.br:8080/jspui/handle/tede/402Leprosy is a chronic infectious disease that mainly affects skin and peripheral nervous system, whose etiologic agent is the bacillus Mycobacterium leprae. Based on the clinical and histopathological characteristics, leprosy can be classified into two polar forms (tuberculoid and lepromatous), three intermediate or borderline forms (borderline-tuberculoid, borderline- borderline and borderline- lepromatous) and two reactional events (Type I and II). This broad spectrum of clinical forms is directly related to cellular immune response, with the influence of Th1, Th2, Th17 and regulatory T cells. Recently, B cells have also been described as important immunoregulatory elements, since they can produce different classes of cytokines and currently subdivided into effector B cells and regulatory B cells. Preliminary results from our group demonstrated that BKO knockout mice exhibit significantly larger bacillary plantar cushions than wild animals (WT), demonstrating the importance of such cells in experimental leprosy. The present study evaluated the expression of cytokines related to the immunopathology of leprosy (IFN-gamma, TNF-alpha, IL-4, IL-17, TGF -beta and IL-10) in the plantar cushions and lymph nodes of the BKO and WT mice. Additionally, to characterize the inflammatory infiltrate, the subpopulations of macrophages M1 and M2 present in the plantar cushions of both groups were phenotyped using the immunohistochemical technique. The results obtained demonstrated that expression of IL-4, IL-10 and TGF-beta cytokines was significantly higher in the BKO plantar cushions when compared to the WT group, but there was no difference in IFN-gamma, TNF-alpha and IL-17. In addition, in the lymph nodes, only IL-17 expression was significantly higher in the WT group. As for the inflammatory infiltrate, the number of M1 macrophages was significantly lower in the BKO group when compared to the WT group, whereas the number of M2 macrophages was significantly higher in the BKO and WT groups when compared to the M1 macrophages. The results obtained in this study demonstrated that the absence of B lymphocytes contribute to the persistence and multiplication of the bacillus, probably due to the increased expression of the IL-4, IL-10 and TGF-beta cytokines, as well as a decrease in the number of M1 macrophages in the inflammatory site.A hanseníase é uma doença infecciosa crônica que afeta principalmente a pele e o sistema nervoso periférico, cujo agente etiológico é o bacilo Mycobacterium leprae. Baseado nas características clínicas e histopatológicas, a hanseníase pode ser classificada em duas formas polares (tuberculóide e virchoviana), três formas intermediárias ou dimorfas (dimorfo-tuberculóide, dimorfo-dimorfo e dimorfo-virchoviano) e dois quadros reacionais (Reações do tipo I e II). Este amplo espectro de formas clínicas está diretamente relacionado a resposta imune celular, com a influência das células Th1, Th2, Th17 e T regulatórias. Recentemente, as células B também têm sido descritas como importantes elementos imunorregulatórios, uma vez que podem produzir diferentes classes de citocinas, sendo atualmente subdivididas em células B efetoras e células B regulatórias. De fato, resultados preliminares do nosso grupo, demonstraram que camundongos nocaute de células B (BKO) apresentam multiplicação bacilar no coxim plantar significativamente maior do que animais selvagens (WT), demonstrando a importância de tais células na hanseníase experimental. Diante dos resultados e visando entender a ação destas células na hanseníase experimental, este estudo avaliou, por Real Time PCR, a expressão de citocinas relacionadas a imunopatologia da hanseníase (IFN-gama, TNF-alfa, IL-4, IL-17, TGF-beta e IL-10) nos coxins plantares e linfonodos dos camundongos BKO e WT. Adicionalmente, para caracterizar o infiltrado inflamatório foram fenotipados, por meio da técnica de imuno-histoquímica, as subpopulações de macrófagos M1 e M2 presentes nos coxins plantares de ambos os grupos. Os resultados obtidos demonstraram que expressão das citocinas IL-4, IL-10 e TGF-beta foram significativamente maior nos coxins plantares do grupo BKO quando comparado ao grupo WT, porém não houve diferença na expressão dos alvos IFN-gama, TNF-alfa e IL-17. Adicionalmente, nos linfonodos, apenas a expressão da IL-17 foi significativamente maior no grupo WT. Quanto ao infiltrado inflamatório, o número de macrófagos M1 foi significativamente menor no grupo BKO quando comparado ao grupo WT, enquanto que o número de macrófagos M2 foi significativamente maior nos grupos BKO e WT, quando comparado com os macrófagos M1. Os resultados obtidos neste estudo demonstraram que a ausência dos linfócitos B contribui para a persistência e multiplicação do bacilo, provavelmente devido ao aumento da expressão das citocinas IL-4, IL-10 e TGF-beta, além da diminuição do número de macrófagos M1 no sítio inflamatório.Submitted by Laudeceia Machado (laudeceia.machado@usc.br) on 2018-05-02T23:36:00Z No. of bitstreams: 1 Avaliacao do papel das celulas B na hanseniase experimental (217507).pdf: 3431079 bytes, checksum: 936a887fa951f561d666b3debc3d3a73 (MD5)Made available in DSpace on 2018-05-02T23:36:00Z (GMT). No. of bitstreams: 1 Avaliacao do papel das celulas B na hanseniase experimental (217507).pdf: 3431079 bytes, checksum: 936a887fa951f561d666b3debc3d3a73 (MD5) Previous issue date: 2018-04-10application/pdfporUniversidade do Sagrado CoraçãoBiologia OralUSCBrasilCiências da Saúde e BiológicasHanseníaseLinfócitos BLeprosyB lymphocyteMycobacterium lepraeCIENCIAS DA SAUDE::ODONTOLOGIAAvaliação do papel das células B na hanseníase experimentalEvaluation of the role of B cells in experimental leprosyinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesis8043334104093724546600600600-753428887677182963-2070498469879244349info:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da USCinstname:Universidade do Sagrado Coração (USC)instacron:USCORIGINALAvaliacao do papel das celulas B na hanseniase experimental (217507).pdfAvaliacao do papel das celulas B na hanseniase experimental (217507).pdfapplication/pdf3431079http://localhost:8080/tede/bitstream/tede/402/2/Avaliacao+do+papel+das+celulas+B+na+hanseniase+experimental+%28217507%29.pdf936a887fa951f561d666b3debc3d3a73MD52LICENSElicense.txtlicense.txttext/plain; charset=utf-82165http://localhost:8080/tede/bitstream/tede/402/1/license.txtbd3efa91386c1718a7f26a329fdcb468MD51tede/4022018-05-02 20:36:00.569oai:localhost: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Biblioteca Digital de Teses e Dissertaçõeshttps://tede2.usc.br:8443/http://tede2.usc.br:8080/oai/requestbiblicorjesu@unisagrado.edu.br||normalizacao@usc.bropendoar:2018-05-02T23:36Biblioteca Digital de Teses e Dissertações da USC - Universidade do Sagrado Coração (USC)false |
dc.title.eng.fl_str_mv |
Avaliação do papel das células B na hanseníase experimental |
dc.title.alternative.eng.fl_str_mv |
Evaluation of the role of B cells in experimental leprosy |
title |
Avaliação do papel das células B na hanseníase experimental |
spellingShingle |
Avaliação do papel das células B na hanseníase experimental Marques, Heloisa Hanseníase Linfócitos B Leprosy B lymphocyte Mycobacterium leprae CIENCIAS DA SAUDE::ODONTOLOGIA |
title_short |
Avaliação do papel das células B na hanseníase experimental |
title_full |
Avaliação do papel das células B na hanseníase experimental |
title_fullStr |
Avaliação do papel das células B na hanseníase experimental |
title_full_unstemmed |
Avaliação do papel das células B na hanseníase experimental |
title_sort |
Avaliação do papel das células B na hanseníase experimental |
author |
Marques, Heloisa |
author_facet |
Marques, Heloisa |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Trombone-Garlet, Ana Paula Favaro |
dc.contributor.advisor1ID.fl_str_mv |
24569954-5 |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/8152853020428952 |
dc.contributor.advisor-co1.fl_str_mv |
Rosa, Patrícia Sammarco |
dc.contributor.advisor-co1ID.fl_str_mv |
063.367.868-62 |
dc.contributor.advisor-co1Lattes.fl_str_mv |
http://lattes.cnpq.br/8870159564860425 |
dc.contributor.authorID.fl_str_mv |
25.697.532-2 191.426.898-99 |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/5983938584153951 |
dc.contributor.author.fl_str_mv |
Marques, Heloisa |
contributor_str_mv |
Trombone-Garlet, Ana Paula Favaro Rosa, Patrícia Sammarco |
dc.subject.por.fl_str_mv |
Hanseníase Linfócitos B |
topic |
Hanseníase Linfócitos B Leprosy B lymphocyte Mycobacterium leprae CIENCIAS DA SAUDE::ODONTOLOGIA |
dc.subject.eng.fl_str_mv |
Leprosy B lymphocyte Mycobacterium leprae |
dc.subject.cnpq.fl_str_mv |
CIENCIAS DA SAUDE::ODONTOLOGIA |
description |
Leprosy is a chronic infectious disease that mainly affects skin and peripheral nervous system, whose etiologic agent is the bacillus Mycobacterium leprae. Based on the clinical and histopathological characteristics, leprosy can be classified into two polar forms (tuberculoid and lepromatous), three intermediate or borderline forms (borderline-tuberculoid, borderline- borderline and borderline- lepromatous) and two reactional events (Type I and II). This broad spectrum of clinical forms is directly related to cellular immune response, with the influence of Th1, Th2, Th17 and regulatory T cells. Recently, B cells have also been described as important immunoregulatory elements, since they can produce different classes of cytokines and currently subdivided into effector B cells and regulatory B cells. Preliminary results from our group demonstrated that BKO knockout mice exhibit significantly larger bacillary plantar cushions than wild animals (WT), demonstrating the importance of such cells in experimental leprosy. The present study evaluated the expression of cytokines related to the immunopathology of leprosy (IFN-gamma, TNF-alpha, IL-4, IL-17, TGF -beta and IL-10) in the plantar cushions and lymph nodes of the BKO and WT mice. Additionally, to characterize the inflammatory infiltrate, the subpopulations of macrophages M1 and M2 present in the plantar cushions of both groups were phenotyped using the immunohistochemical technique. The results obtained demonstrated that expression of IL-4, IL-10 and TGF-beta cytokines was significantly higher in the BKO plantar cushions when compared to the WT group, but there was no difference in IFN-gamma, TNF-alpha and IL-17. In addition, in the lymph nodes, only IL-17 expression was significantly higher in the WT group. As for the inflammatory infiltrate, the number of M1 macrophages was significantly lower in the BKO group when compared to the WT group, whereas the number of M2 macrophages was significantly higher in the BKO and WT groups when compared to the M1 macrophages. The results obtained in this study demonstrated that the absence of B lymphocytes contribute to the persistence and multiplication of the bacillus, probably due to the increased expression of the IL-4, IL-10 and TGF-beta cytokines, as well as a decrease in the number of M1 macrophages in the inflammatory site. |
publishDate |
2018 |
dc.date.accessioned.fl_str_mv |
2018-05-02T23:36:00Z |
dc.date.issued.fl_str_mv |
2018-04-10 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/doctoralThesis |
format |
doctoralThesis |
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publishedVersion |
dc.identifier.citation.fl_str_mv |
MARQUES, Heloisa. Avaliação do papel das células B na hanseníase experimental. 2018. 76 f. Tese (Doutorado em Biologia Oral) - Universidade do Sagrado Coração, Bauru, 2018. |
dc.identifier.uri.fl_str_mv |
http://tede2.usc.br:8080/jspui/handle/tede/402 |
identifier_str_mv |
MARQUES, Heloisa. Avaliação do papel das células B na hanseníase experimental. 2018. 76 f. Tese (Doutorado em Biologia Oral) - Universidade do Sagrado Coração, Bauru, 2018. |
url |
http://tede2.usc.br:8080/jspui/handle/tede/402 |
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por |
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por |
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Universidade do Sagrado Coração |
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Biologia Oral |
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USC |
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Brasil |
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Ciências da Saúde e Biológicas |
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Universidade do Sagrado Coração |
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