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Ana Maria Caetano de Fariahttp://lattes.cnpq.br/2268635568464108Rafael Machado RezendeMaria de Fátima Martins HortaFabiana Simão MachadoAna Paula FerreiraJoana Ferreira Amaralhttp://lattes.cnpq.br/0104230117686704Mauro Andrade de Freitas Guimarães2021-02-01T15:07:34Z2021-02-01T15:07:34Z2017-06-01http://hdl.handle.net/1843/34913A esclerose múltipla é uma doença autoimune, de fundo genético, que afeta o sistema nervoso central. As manifestações iniciais são derivadas de respostas imunológicas intensas que afetam principalmente a substância branca do cérebro e da medula espinhal, sendo seguida por uma fase crônica com caráter neurodegenerativo. Diante da complexidade da doença e da dificuldade de tratamento, nosso grupo de pesquisa tem estudado alternativas imunorregulatórias capazes de reduzir os sinais clínicos da doença que apresentem poucos ou nenhum efeitos adversos. Previamente a esse trabalho, utilizamo-nos de um protocolo para indução da tolerância oral a HPS65 produzida pela bactéria recombinante Lactococcus lactis atrevas do qual obtivemos bons resultados na prevenção dos sintomas da encefalomielite autoimune experimental (EAE) induzida em camundongos C57BL/6 pela imunização com o antígeno mieliníco MOG. No presente trabalho o mesmo protocolo foi utilizado para o tratamento da EAE depois da sua indução. Camundongos imunizados com MOG receberam por via oral a cepa Lactococcus lactis produtora da proteína de choque térmico HPS65, durante cinco dias. O tratamento foi eficiente na redução do índice clínico da EAE da mesma formar que na prevenção da doença. Foi observado por análise histológica e microscopia intravital que o tratamento inibiu o recrutamento de leucócitos para a medula espinhal tanto no parênquima quanto nos vasos sanguíneos que irrigam as meninges. Nos órgãos linfoides secundários, houve um aumento da frequência das células T reguladoras, principalmente aquelas que expressam a forma da embrana citocina TGF-B (latente associete peptide - LAP). Não houve alteração na frequência de linfócitos T CD4+ ativados nos animais tratados indicando que o mecanismo de inibição não envolve imunossupressão.Multiple sclerosis is a genetic and autoimmune disease that affects the central nervous system. The initial manifestations is an intense immune responses that primainly affect the white matter of the brain and spinal cord, followed by a chronic phase with a neurodegenerative character.Because of the complexity of the disease and the difficulty to treat, has been testing therapeutic alternatives that wold modulate the disease development presenting minimal sides effects. In a previus study, we used a protocol for the induction of oral tolerance using a recombinant HPS65 producing Lactococcus lactis and we obtained good results in the prevention of experimental autoimmune encephalomyelitis (EAE), induced in C57BL / 6 mice by MOG immunization. In the present study, the same protocol was used for the treatment. In the present study, mice received orally HPS65-producing Lactococcus lactis strain for five days after disease induction. The treatment was as efficient in reducing the clinical score of EAE as the prevention protocol. Using histologicalIt analysis and intravital microscopy, we observed that the treatment inhibited the recruitment of leukocytes to the spinal cord, both in the parenchyma and in the blood vessels that irrigate the meninges. In the secondary lymphoid organs, there was an increase in regulatory T cells, especially those that express the membrane form of the cytokine TGF-B in the membrane (LAP). This effect occurred with no alteretion in the frequency of ativadet lynphocytes indicating that there immunoregulation was not associated with immunosuppressive.CNPq - Conselho Nacional de Desenvolvimento Científico e TecnológicoFAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas GeraisCAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorporUniversidade Federal de Minas GeraisPrograma de Pós-Graduação em Bioquímica e ImunologiaUFMGBrasilICB - DEPARTAMENTO DE BIOQUÍMICA E IMUNOLOGIAhttp://creativecommons.org/licenses/by-nc-nd/3.0/pt/info:eu-repo/semantics/openAccessEncefalomielite autoimune experimentalLactococcus lactisCélulas precursoras de linfócitos TEncefalomielite autoimune experimentalTratamentoL.lactis produtor de HSP65ImunorregulaçãoLactococcus lactis produtor de HSP65 inibe a encefalomielite autoimune experimental murina previnindo a migração de células T para a medula espinhalinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisreponame:Repositório Institucional da UFMGinstname:Universidade Federal de Minas Gerais (UFMG)instacron:UFMGORIGINALTese Mauro Guimaraes.pdfTese Mauro Guimaraes.pdfapplication/pdf21208496https://repositorio.ufmg.br/bitstream/1843/34913/1/Tese%20Mauro%20Guimaraes.pdf2f8efb878d8430e6ef5ec7f58d2e612bMD51CC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; charset=utf-8811https://repositorio.ufmg.br/bitstream/1843/34913/2/license_rdfcfd6801dba008cb6adbd9838b81582abMD52LICENSElicense.txtlicense.txttext/plain; charset=utf-82119https://repositorio.ufmg.br/bitstream/1843/34913/3/license.txt34badce4be7e31e3adb4575ae96af679MD531843/349132021-02-01 12:07:34.614oai:repositorio.ufmg.br:1843/34913TElDRU7Dh0EgREUgRElTVFJJQlVJw4fDg08gTsODTy1FWENMVVNJVkEgRE8gUkVQT1NJVMOTUklPIElOU1RJVFVDSU9OQUwgREEgVUZNRwoKQ29tIGEgYXByZXNlbnRhw6fDo28gZGVzdGEgbGljZW7Dp2EsIHZvY8OqIChvIGF1dG9yIChlcykgb3UgbyB0aXR1bGFyIGRvcyBkaXJlaXRvcyBkZSBhdXRvcikgY29uY2VkZSBhbyBSZXBvc2l0w7NyaW8gSW5zdGl0dWNpb25hbCBkYSBVRk1HIChSSS1VRk1HKSBvIGRpcmVpdG8gbsOjbyBleGNsdXNpdm8gZSBpcnJldm9nw6F2ZWwgZGUgcmVwcm9kdXppciBlL291IGRpc3RyaWJ1aXIgYSBzdWEgcHVibGljYcOnw6NvIChpbmNsdWluZG8gbyByZXN1bW8pIHBvciB0b2RvIG8gbXVuZG8gbm8gZm9ybWF0byBpbXByZXNzbyBlIGVsZXRyw7RuaWNvIGUgZW0gcXVhbHF1ZXIgbWVpbywgaW5jbHVpbmRvIG9zIGZvcm1hdG9zIMOhdWRpbyBvdSB2w61kZW8uCgpWb2PDqiBkZWNsYXJhIHF1ZSBjb25oZWNlIGEgcG9sw610aWNhIGRlIGNvcHlyaWdodCBkYSBlZGl0b3JhIGRvIHNldSBkb2N1bWVudG8gZSBxdWUgY29uaGVjZSBlIGFjZWl0YSBhcyBEaXJldHJpemVzIGRvIFJJLVVGTUcuCgpWb2PDqiBjb25jb3JkYSBxdWUgbyBSZXBvc2l0w7NyaW8gSW5zdGl0dWNpb25hbCBkYSBVRk1HIHBvZGUsIHNlbSBhbHRlcmFyIG8gY29udGXDumRvLCB0cmFuc3BvciBhIHN1YSBwdWJsaWNhw6fDo28gcGFyYSBxdWFscXVlciBtZWlvIG91IGZvcm1hdG8gcGFyYSBmaW5zIGRlIHByZXNlcnZhw6fDo28uCgpWb2PDqiB0YW1iw6ltIGNvbmNvcmRhIHF1ZSBvIFJlcG9zaXTDs3JpbyBJbnN0aXR1Y2lvbmFsIGRhIFVGTUcgcG9kZSBtYW50ZXIgbWFpcyBkZSB1bWEgY8OzcGlhIGRlIHN1YSBwdWJsaWNhw6fDo28gcGFyYSBmaW5zIGRlIHNlZ3VyYW7Dp2EsIGJhY2stdXAgZSBwcmVzZXJ2YcOnw6NvLgoKVm9jw6ogZGVjbGFyYSBxdWUgYSBzdWEgcHVibGljYcOnw6NvIMOpIG9yaWdpbmFsIGUgcXVlIHZvY8OqIHRlbSBvIHBvZGVyIGRlIGNvbmNlZGVyIG9zIGRpcmVpdG9zIGNvbnRpZG9zIG5lc3RhIGxpY2Vuw6dhLiBWb2PDqiB0YW1iw6ltIGRlY2xhcmEgcXVlIG8gZGVww7NzaXRvIGRlIHN1YSBwdWJsaWNhw6fDo28gbsOjbywgcXVlIHNlamEgZGUgc2V1IGNvbmhlY2ltZW50bywgaW5mcmluZ2UgZGlyZWl0b3MgYXV0b3JhaXMgZGUgbmluZ3XDqW0uCgpDYXNvIGEgc3VhIHB1YmxpY2HDp8OjbyBjb250ZW5oYSBtYXRlcmlhbCBxdWUgdm9jw6ogbsOjbyBwb3NzdWkgYSB0aXR1bGFyaWRhZGUgZG9zIGRpcmVpdG9zIGF1dG9yYWlzLCB2b2PDqiBkZWNsYXJhIHF1ZSBvYnRldmUgYSBwZXJtaXNzw6NvIGlycmVzdHJpdGEgZG8gZGV0ZW50b3IgZG9zIGRpcmVpdG9zIGF1dG9yYWlzIHBhcmEgY29uY2VkZXIgYW8gUmVwb3NpdMOzcmlvIEluc3RpdHVjaW9uYWwgZGEgVUZNRyBvcyBkaXJlaXRvcyBhcHJlc2VudGFkb3MgbmVzdGEgbGljZW7Dp2EsIGUgcXVlIGVzc2UgbWF0ZXJpYWwgZGUgcHJvcHJpZWRhZGUgZGUgdGVyY2Vpcm9zIGVzdMOhIGNsYXJhbWVudGUgaWRlbnRpZmljYWRvIGUgcmVjb25oZWNpZG8gbm8gdGV4dG8gb3Ugbm8gY29udGXDumRvIGRhIHB1YmxpY2HDp8OjbyBvcmEgZGVwb3NpdGFkYS4KCkNBU08gQSBQVUJMSUNBw4fDg08gT1JBIERFUE9TSVRBREEgVEVOSEEgU0lETyBSRVNVTFRBRE8gREUgVU0gUEFUUk9Dw41OSU8gT1UgQVBPSU8gREUgVU1BIEFHw4pOQ0lBIERFIEZPTUVOVE8gT1UgT1VUUk8gT1JHQU5JU01PLCBWT0PDiiBERUNMQVJBIFFVRSBSRVNQRUlUT1UgVE9ET1MgRSBRVUFJU1FVRVIgRElSRUlUT1MgREUgUkVWSVPDg08gQ09NTyBUQU1Cw4lNIEFTIERFTUFJUyBPQlJJR0HDh8OVRVMgRVhJR0lEQVMgUE9SIENPTlRSQVRPIE9VIEFDT1JETy4KCk8gUmVwb3NpdMOzcmlvIEluc3RpdHVjaW9uYWwgZGEgVUZNRyBzZSBjb21wcm9tZXRlIGEgaWRlbnRpZmljYXIgY2xhcmFtZW50ZSBvIHNldSBub21lKHMpIG91IG8ocykgbm9tZXMocykgZG8ocykgZGV0ZW50b3IoZXMpIGRvcyBkaXJlaXRvcyBhdXRvcmFpcyBkYSBwdWJsaWNhw6fDo28sIGUgbsOjbyBmYXLDoSBxdWFscXVlciBhbHRlcmHDp8OjbywgYWzDqW0gZGFxdWVsYXMgY29uY2VkaWRhcyBwb3IgZXN0YSBsaWNlbsOnYS4KCg==Repositório InstitucionalPUBhttps://repositorio.ufmg.br/oaiopendoar:2021-02-01T15:07:34Repositório Institucional da UFMG - Universidade Federal de Minas Gerais (UFMG)false
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