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Rodrigo Correa Oliveirahttp://lattes.cnpq.br/8712666530716107Lis Ribeiro do Valle AntonelliDaniel Santos MansurAna Maria Caetano de FariaCláudio Antônio Bonjardimhttp://lattes.cnpq.br/1391461081338646Eduardo Augusto dos Santos Moreira Silva2021-02-01T10:48:22Z2021-02-01T10:48:22Z2014-05-17http://hdl.handle.net/1843/34912Vaccinia virus (VACV) é o agente causador de uma importante zoonose que afeta o gado bovino e seres humanos em várias regiões do Brasil. Pouco se sabe acerca da resposta imunológica contra uma infecção natural pelo VACV, mas tanto a resposta imune inata quanto a adaptativa são importantes. As células NK, nesse contexto, constituem um elemento importante na resposta imune inata contra o VACV, sendo os receptores citotóxicos naturais (NCR) figuram entre os receptores mais importantes das células NK no reconhecimento das células infectadas pelo VACV.Existem poucos estudos acerca da participação desses NCRs e outros receptores de ativação das células NK. Desse modo, o presente estudo tem como objetivo descrever e comparar o fenótipo das células NK de indivíduos previamente vacinados com indivíduos previamente infectados pelo VACV, após uma estimulação in vitro com VACV. Nossos dados sugerem que a estimulação com o VACV gera uma resposta citotóxica pelas células NK, evidenciadas pelo aumento dos NCRs em indivíduos previamente infectados (vacinados ou não) e nos indivíduos não infectados vacinados, quando comparados com indivíduos não infectados não vacinados. No entanto, os processos de degranulação e secreção parecem estar inibidos nos indivíduos infectados (vacinados ou não) e nos indivíduos não infectados vacinados, quando comparados com indivíduos não infectados não vacinados. Demonstrou-se que a estimulação com o VACV gera uma diminuição no percentual de células expressando perforina, granzima A e CD107a, mas causa um aumento no percentual de CD94, CD161 e Granzima B nos indivíduos infectados (vacinados ou não) e nos indivíduos não infectados vacinados, quando comparados com indivíduos não infectados não vacinados. Além disso, o percentual de células IFN-g + foi significativamente menor em indivíduos não infectados não vacinados, comparados aos indivíduos infectados e não infectados vacinados. Em relação ao TNF-a houve aumento do percentual de células TNF-a +, nos indivíduos infectados (vacinados ou não) e nos indivíduos não infectados vacinados, quando comparados com indivíduos não infectados não vacinados.Vaccinia virus (VACV) is the causative agent of a zoonotic infection that affects cattle and humans in many regions of Brazil. Little is known about the human immunological response against VACV natural infection, but it is clear that both the innate and adaptative responses are important. It seems that the natural cytotoxicity receptors NKp30, NKp44, and NKp46 are the most important NK cell receptors for the recognition of the VACV-infected target cell. At this moment, there are few studies that analyze the profile of natural killer after a natural VACV infection. So, the present study compares the profile of NK cells in an in vitro re-exposure by Vaccinia virus (VACV), in groups that have had a previous vaccination or natural infection. A short stimulation with UV-inactivated VACV was performed. Our data suggests that stimulation with VACV triggers a cytotoxic response by NK cells marked by an increase of NCRs in infected (vaccinated and unvaccinated) subjects and in non-infected vaccinated patients, when compared with non-infected unvaccinated individuals. However, the degranulation and secretion processes are inhibited in infected (vaccinated and unvaccinated) subjects and in the non-infected vaccinated patients, when compared with non-infected unvaccinated individuals. We demonstrated that stimulation with VACV downregulates the percentage of expression of Perforin, Granzyme A, and CD107a, but upregulate CD94, CD161 e Granzyme B in infected (vaccinated and unvaccinated) subjects and in non-infected vaccinated patients, when compared with non-infected unvaccinated individuals. Furthermore, the percentage of IFN-g + NK cells was significantly lower in non-infected unvaccinated subjects, when compared with infected (vaccinated and unvaccinated) and non-infected vaccinated individuals. Our results also show that the percentage of TNF-a + NK cells was significantly higher in infected (vaccinated and unvaccinated) subjects and in non-infected vaccinated patients, when compared with non-infected unvaccinated individuals, after in vitro stimulation with UV-inactivated VACV.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/openAccessVírus vacciniaInfecções por poxviridaeInfecçõesZoonosesVacina antivariólicaVaccinia virusInfecções por PoxvirusInfecçõesZoonosesVacina contra a varíolaPerfil fenotípico das células NK em uma reexposição viral, in vitro, após uma infecção humana natural prévia pelo Vaccinia virusinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisreponame:Repositório Institucional da UFMGinstname:Universidade Federal de Minas Gerais (UFMG)instacron:UFMGORIGINALTese Completa Eduardo.pdfTese Completa Eduardo.pdfapplication/pdf13682537https://repositorio.ufmg.br/bitstream/1843/34912/1/Tese%20Completa%20Eduardo.pdf8b92cf1d07ad2d9a4b256f17d4f4dfd4MD51CC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; charset=utf-8811https://repositorio.ufmg.br/bitstream/1843/34912/2/license_rdfcfd6801dba008cb6adbd9838b81582abMD52LICENSElicense.txtlicense.txttext/plain; charset=utf-82119https://repositorio.ufmg.br/bitstream/1843/34912/3/license.txt34badce4be7e31e3adb4575ae96af679MD531843/349122021-02-01 07:48:22.946oai:repositorio.ufmg.br:1843/34912TElDRU7Dh0EgREUgRElTVFJJQlVJw4fDg08gTsODTy1FWENMVVNJVkEgRE8gUkVQT1NJVMOTUklPIElOU1RJVFVDSU9OQUwgREEgVUZNRwoKQ29tIGEgYXByZXNlbnRhw6fDo28gZGVzdGEgbGljZW7Dp2EsIHZvY8OqIChvIGF1dG9yIChlcykgb3UgbyB0aXR1bGFyIGRvcyBkaXJlaXRvcyBkZSBhdXRvcikgY29uY2VkZSBhbyBSZXBvc2l0w7NyaW8gSW5zdGl0dWNpb25hbCBkYSBVRk1HIChSSS1VRk1HKSBvIGRpcmVpdG8gbsOjbyBleGNsdXNpdm8gZSBpcnJldm9nw6F2ZWwgZGUgcmVwcm9kdXppciBlL291IGRpc3RyaWJ1aXIgYSBzdWEgcHVibGljYcOnw6NvIChpbmNsdWluZG8gbyByZXN1bW8pIHBvciB0b2RvIG8gbXVuZG8gbm8gZm9ybWF0byBpbXByZXNzbyBlIGVsZXRyw7RuaWNvIGUgZW0gcXVhbHF1ZXIgbWVpbywgaW5jbHVpbmRvIG9zIGZvcm1hdG9zIMOhdWRpbyBvdSB2w61kZW8uCgpWb2PDqiBkZWNsYXJhIHF1ZSBjb25oZWNlIGEgcG9sw610aWNhIGRlIGNvcHlyaWdodCBkYSBlZGl0b3JhIGRvIHNldSBkb2N1bWVudG8gZSBxdWUgY29uaGVjZSBlIGFjZWl0YSBhcyBEaXJldHJpemVzIGRvIFJJLVVGTUcuCgpWb2PDqiBjb25jb3JkYSBxdWUgbyBSZXBvc2l0w7NyaW8gSW5zdGl0dWNpb25hbCBkYSBVRk1HIHBvZGUsIHNlbSBhbHRlcmFyIG8gY29udGXDumRvLCB0cmFuc3BvciBhIHN1YSBwdWJsaWNhw6fDo28gcGFyYSBxdWFscXVlciBtZWlvIG91IGZvcm1hdG8gcGFyYSBmaW5zIGRlIHByZXNlcnZhw6fDo28uCgpWb2PDqiB0YW1iw6ltIGNvbmNvcmRhIHF1ZSBvIFJlcG9zaXTDs3JpbyBJbnN0aXR1Y2lvbmFsIGRhIFVGTUcgcG9kZSBtYW50ZXIgbWFpcyBkZSB1bWEgY8OzcGlhIGRlIHN1YSBwdWJsaWNhw6fDo28gcGFyYSBmaW5zIGRlIHNlZ3VyYW7Dp2EsIGJhY2stdXAgZSBwcmVzZXJ2YcOnw6NvLgoKVm9jw6ogZGVjbGFyYSBxdWUgYSBzdWEgcHVibGljYcOnw6NvIMOpIG9yaWdpbmFsIGUgcXVlIHZvY8OqIHRlbSBvIHBvZGVyIGRlIGNvbmNlZGVyIG9zIGRpcmVpdG9zIGNvbnRpZG9zIG5lc3RhIGxpY2Vuw6dhLiBWb2PDqiB0YW1iw6ltIGRlY2xhcmEgcXVlIG8gZGVww7NzaXRvIGRlIHN1YSBwdWJsaWNhw6fDo28gbsOjbywgcXVlIHNlamEgZGUgc2V1IGNvbmhlY2ltZW50bywgaW5mcmluZ2UgZGlyZWl0b3MgYXV0b3JhaXMgZGUgbmluZ3XDqW0uCgpDYXNvIGEgc3VhIHB1YmxpY2HDp8OjbyBjb250ZW5oYSBtYXRlcmlhbCBxdWUgdm9jw6ogbsOjbyBwb3NzdWkgYSB0aXR1bGFyaWRhZGUgZG9zIGRpcmVpdG9zIGF1dG9yYWlzLCB2b2PDqiBkZWNsYXJhIHF1ZSBvYnRldmUgYSBwZXJtaXNzw6NvIGlycmVzdHJpdGEgZG8gZGV0ZW50b3IgZG9zIGRpcmVpdG9zIGF1dG9yYWlzIHBhcmEgY29uY2VkZXIgYW8gUmVwb3NpdMOzcmlvIEluc3RpdHVjaW9uYWwgZGEgVUZNRyBvcyBkaXJlaXRvcyBhcHJlc2VudGFkb3MgbmVzdGEgbGljZW7Dp2EsIGUgcXVlIGVzc2UgbWF0ZXJpYWwgZGUgcHJvcHJpZWRhZGUgZGUgdGVyY2Vpcm9zIGVzdMOhIGNsYXJhbWVudGUgaWRlbnRpZmljYWRvIGUgcmVjb25oZWNpZG8gbm8gdGV4dG8gb3Ugbm8gY29udGXDumRvIGRhIHB1YmxpY2HDp8OjbyBvcmEgZGVwb3NpdGFkYS4KCkNBU08gQSBQVUJMSUNBw4fDg08gT1JBIERFUE9TSVRBREEgVEVOSEEgU0lETyBSRVNVTFRBRE8gREUgVU0gUEFUUk9Dw41OSU8gT1UgQVBPSU8gREUgVU1BIEFHw4pOQ0lBIERFIEZPTUVOVE8gT1UgT1VUUk8gT1JHQU5JU01PLCBWT0PDiiBERUNMQVJBIFFVRSBSRVNQRUlUT1UgVE9ET1MgRSBRVUFJU1FVRVIgRElSRUlUT1MgREUgUkVWSVPDg08gQ09NTyBUQU1Cw4lNIEFTIERFTUFJUyBPQlJJR0HDh8OVRVMgRVhJR0lEQVMgUE9SIENPTlRSQVRPIE9VIEFDT1JETy4KCk8gUmVwb3NpdMOzcmlvIEluc3RpdHVjaW9uYWwgZGEgVUZNRyBzZSBjb21wcm9tZXRlIGEgaWRlbnRpZmljYXIgY2xhcmFtZW50ZSBvIHNldSBub21lKHMpIG91IG8ocykgbm9tZXMocykgZG8ocykgZGV0ZW50b3IoZXMpIGRvcyBkaXJlaXRvcyBhdXRvcmFpcyBkYSBwdWJsaWNhw6fDo28sIGUgbsOjbyBmYXLDoSBxdWFscXVlciBhbHRlcmHDp8OjbywgYWzDqW0gZGFxdWVsYXMgY29uY2VkaWRhcyBwb3IgZXN0YSBsaWNlbsOnYS4KCg==Repositório InstitucionalPUBhttps://repositorio.ufmg.br/oaiopendoar:2021-02-01T10:48:22Repositório Institucional da UFMG - Universidade Federal de Minas Gerais (UFMG)false
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