Avaliação do papel das células B na hanseníase experimental

Detalhes bibliográficos
Autor(a) principal: Marques, Heloisa
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.
id USC_c670c766f7306dcc0bc07140d05ae0dc
oai_identifier_str oai:localhost:tede/402
network_acronym_str USC
network_name_str Biblioteca Digital de Teses e Dissertações da USC
repository_id_str
spelling 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:tede/402Tk9UQTogQ09MT1FVRSBBUVVJIEEgU1VBIFBSw5NQUklBIExJQ0VOw4dBCkVzdGEgbGljZW7Dp2EgZGUgZXhlbXBsbyDDqSBmb3JuZWNpZGEgYXBlbmFzIHBhcmEgZmlucyBpbmZvcm1hdGl2b3MuCgpMSUNFTsOHQSBERSBESVNUUklCVUnDh8ODTyBOw4NPLUVYQ0xVU0lWQQoKQ29tIGEgYXByZXNlbnRhw6fDo28gZGVzdGEgbGljZW7Dp2EsIHZvY8OqIChvIGF1dG9yIChlcykgb3UgbyB0aXR1bGFyIGRvcyBkaXJlaXRvcyBkZSBhdXRvcikgY29uY2VkZSDDoCBVbml2ZXJzaWRhZGUgClhYWCAoU2lnbGEgZGEgVW5pdmVyc2lkYWRlKSBvIGRpcmVpdG8gbsOjby1leGNsdXNpdm8gZGUgcmVwcm9kdXppciwgIHRyYWR1emlyIChjb25mb3JtZSBkZWZpbmlkbyBhYmFpeG8pLCBlL291IApkaXN0cmlidWlyIGEgc3VhIHRlc2Ugb3UgZGlzc2VydGHDp8OjbyAoaW5jbHVpbmRvIG8gcmVzdW1vKSBwb3IgdG9kbyBvIG11bmRvIG5vIGZvcm1hdG8gaW1wcmVzc28gZSBlbGV0csO0bmljbyBlIAplbSBxdWFscXVlciBtZWlvLCBpbmNsdWluZG8gb3MgZm9ybWF0b3Mgw6F1ZGlvIG91IHbDrWRlby4KClZvY8OqIGNvbmNvcmRhIHF1ZSBhIFNpZ2xhIGRlIFVuaXZlcnNpZGFkZSBwb2RlLCBzZW0gYWx0ZXJhciBvIGNvbnRlw7pkbywgdHJhbnNwb3IgYSBzdWEgdGVzZSBvdSBkaXNzZXJ0YcOnw6NvIApwYXJhIHF1YWxxdWVyIG1laW8gb3UgZm9ybWF0byBwYXJhIGZpbnMgZGUgcHJlc2VydmHDp8Ojby4KClZvY8OqIHRhbWLDqW0gY29uY29yZGEgcXVlIGEgU2lnbGEgZGUgVW5pdmVyc2lkYWRlIHBvZGUgbWFudGVyIG1haXMgZGUgdW1hIGPDs3BpYSBhIHN1YSB0ZXNlIG91IApkaXNzZXJ0YcOnw6NvIHBhcmEgZmlucyBkZSBzZWd1cmFuw6dhLCBiYWNrLXVwIGUgcHJlc2VydmHDp8Ojby4KClZvY8OqIGRlY2xhcmEgcXVlIGEgc3VhIHRlc2Ugb3UgZGlzc2VydGHDp8OjbyDDqSBvcmlnaW5hbCBlIHF1ZSB2b2PDqiB0ZW0gbyBwb2RlciBkZSBjb25jZWRlciBvcyBkaXJlaXRvcyBjb250aWRvcyAKbmVzdGEgbGljZW7Dp2EuIFZvY8OqIHRhbWLDqW0gZGVjbGFyYSBxdWUgbyBkZXDDs3NpdG8gZGEgc3VhIHRlc2Ugb3UgZGlzc2VydGHDp8OjbyBuw6NvLCBxdWUgc2VqYSBkZSBzZXUgCmNvbmhlY2ltZW50bywgaW5mcmluZ2UgZGlyZWl0b3MgYXV0b3JhaXMgZGUgbmluZ3XDqW0uCgpDYXNvIGEgc3VhIHRlc2Ugb3UgZGlzc2VydGHDp8OjbyBjb250ZW5oYSBtYXRlcmlhbCBxdWUgdm9jw6ogbsOjbyBwb3NzdWkgYSB0aXR1bGFyaWRhZGUgZG9zIGRpcmVpdG9zIGF1dG9yYWlzLCB2b2PDqiAKZGVjbGFyYSBxdWUgb2J0ZXZlIGEgcGVybWlzc8OjbyBpcnJlc3RyaXRhIGRvIGRldGVudG9yIGRvcyBkaXJlaXRvcyBhdXRvcmFpcyBwYXJhIGNvbmNlZGVyIMOgIFNpZ2xhIGRlIFVuaXZlcnNpZGFkZSAKb3MgZGlyZWl0b3MgYXByZXNlbnRhZG9zIG5lc3RhIGxpY2Vuw6dhLCBlIHF1ZSBlc3NlIG1hdGVyaWFsIGRlIHByb3ByaWVkYWRlIGRlIHRlcmNlaXJvcyBlc3TDoSBjbGFyYW1lbnRlIAppZGVudGlmaWNhZG8gZSByZWNvbmhlY2lkbyBubyB0ZXh0byBvdSBubyBjb250ZcO6ZG8gZGEgdGVzZSBvdSBkaXNzZXJ0YcOnw6NvIG9yYSBkZXBvc2l0YWRhLgoKQ0FTTyBBIFRFU0UgT1UgRElTU0VSVEHDh8ODTyBPUkEgREVQT1NJVEFEQSBURU5IQSBTSURPIFJFU1VMVEFETyBERSBVTSBQQVRST0PDjU5JTyBPVSAKQVBPSU8gREUgVU1BIEFHw4pOQ0lBIERFIEZPTUVOVE8gT1UgT1VUUk8gT1JHQU5JU01PIFFVRSBOw4NPIFNFSkEgQSBTSUdMQSBERSAKVU5JVkVSU0lEQURFLCBWT0PDiiBERUNMQVJBIFFVRSBSRVNQRUlUT1UgVE9ET1MgRSBRVUFJU1FVRVIgRElSRUlUT1MgREUgUkVWSVPDg08gQ09NTyAKVEFNQsOJTSBBUyBERU1BSVMgT0JSSUdBw4fDlUVTIEVYSUdJREFTIFBPUiBDT05UUkFUTyBPVSBBQ09SRE8uCgpBIFNpZ2xhIGRlIFVuaXZlcnNpZGFkZSBzZSBjb21wcm9tZXRlIGEgaWRlbnRpZmljYXIgY2xhcmFtZW50ZSBvIHNldSBub21lIChzKSBvdSBvKHMpIG5vbWUocykgZG8ocykgCmRldGVudG9yKGVzKSBkb3MgZGlyZWl0b3MgYXV0b3JhaXMgZGEgdGVzZSBvdSBkaXNzZXJ0YcOnw6NvLCBlIG7Do28gZmFyw6EgcXVhbHF1ZXIgYWx0ZXJhw6fDo28sIGFsw6ltIGRhcXVlbGFzIApjb25jZWRpZGFzIHBvciBlc3RhIGxpY2Vuw6dhLgo=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
status_str 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
dc.language.iso.fl_str_mv por
language por
dc.relation.program.fl_str_mv 8043334104093724546
dc.relation.confidence.fl_str_mv 600
600
600
dc.relation.department.fl_str_mv -753428887677182963
dc.relation.cnpq.fl_str_mv -2070498469879244349
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Universidade do Sagrado Coração
dc.publisher.program.fl_str_mv Biologia Oral
dc.publisher.initials.fl_str_mv USC
dc.publisher.country.fl_str_mv Brasil
dc.publisher.department.fl_str_mv Ciências da Saúde e Biológicas
publisher.none.fl_str_mv Universidade do Sagrado Coração
dc.source.none.fl_str_mv reponame:Biblioteca Digital de Teses e Dissertações da USC
instname:Universidade do Sagrado Coração (USC)
instacron:USC
instname_str Universidade do Sagrado Coração (USC)
instacron_str USC
institution USC
reponame_str Biblioteca Digital de Teses e Dissertações da USC
collection Biblioteca Digital de Teses e Dissertações da USC
bitstream.url.fl_str_mv http://localhost:8080/tede/bitstream/tede/402/2/Avaliacao+do+papel+das+celulas+B+na+hanseniase+experimental+%28217507%29.pdf
http://localhost:8080/tede/bitstream/tede/402/1/license.txt
bitstream.checksum.fl_str_mv 936a887fa951f561d666b3debc3d3a73
bd3efa91386c1718a7f26a329fdcb468
bitstream.checksumAlgorithm.fl_str_mv MD5
MD5
repository.name.fl_str_mv Biblioteca Digital de Teses e Dissertações da USC - Universidade do Sagrado Coração (USC)
repository.mail.fl_str_mv biblicorjesu@unisagrado.edu.br||normalizacao@usc.br
_version_ 1831413134104985600