Avaliação de genes relacionados à hipóxia associados à resposta imune inata de pacientes com tuberculose pulmonar ativa e latente
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Biblioteca Digital de Teses e Dissertações da UFMA |
Texto Completo: | https://tedebc.ufma.br/jspui/handle/tede/tede/3538 |
Resumo: | Mycobacterium tuberculosis (Mtb) is an intracellular pathogen, the causative agent of Tuberculosis (TB), which infects a large part of the world's population. About 90-95% of individuals infected with Mtb develop latent tuberculosis infection (LTBI), characterized by the formation of a structure called a granuloma, which maintains Mtb bacilli within a set of defense cells. The granuloma is considered hypoxic, and the response to hypoxia is regulated by the hypoxia-induced factor - HIF-1α, which has been associated with several infections, including bacterial ones. In addition to the hypoxia response, other mechanisms involved in active infection may contribute to the establishment of latent Mtb infection. The present study investigated how HIF-1α interferes in the innate immune response of individuals with active or latent infection. Therefore, patients with active pulmonary TB, before the start of treatment, individuals with latent tuberculosis infection (LTBI), who had PPD+ and IGRAs+ and healthy individuals were recruited. Expression of cytokines (IL-15, IL-18, IL-6 and TNF-α) and specific transcription factors (A20 and HIF-1α) that mediate mechanisms of the immune response in patients with active pulmonary TB, LTBI and healthy controls was performed. In addition, the activation of the vitamin D-dependent antimicrobial pathway, which is active by pro-inflammatory cytokines, was analyzed. IL-15 expression was decreased in LTBI subjects and active TB patients, while IL-18 expression was similar between LTBI subjects and healthy controls, both cytokines converge for vitamin D activation, which did not show a significant decrease. The expression of TNF-α and IL-6 were also lower in LTBI subjects. Regarding the transcription factors analyzed, there was a decrease in A20 and HIF-1α. The blockade of HIF-1α in PBMC of individuals with LTBI led to a decrease in the activation of phosphorylated NF-κB and an increase in the production of TNF-α, which may be determinant for the individual's latency condition. The decrease in cytokine production is relevant to keep the infection latent and influence the activation of the NF-κB signaling pathway. The results of this study demonstrate that LTBI is multifactorial, and several factors contribute to its establishment in the host. |
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SOUSA, Eduardo Martins dehttp://lattes.cnpq.br/4448263553675550PEREIRA, Paulo Vitor Soeirohttp://lattes.cnpq.br/7281767698416958SOUSA, Eduardo Martins dehttp://lattes.cnpq.br/4448263553675550SANTOS, Ana Paula Silva de Azevedo doshttp://lattes.cnpq.br/8224124082144965LIBERIO, Rosane Nassar Meireles Guerrahttp://lattes.cnpq.br/2316192786452127COSTA, Adeliane Castrohttp://lattes.cnpq.br/9373163292240939http://lattes.cnpq.br/2488628088138033REZENDE, Aline de Oliveira2022-04-28T14:27:58Z2021-11-22REZENDE, Aline de Oliveira. Avaliação de genes relacionados à hipóxia associados à resposta imune inata de pacientes com tuberculose pulmonar ativa e latente. 2021. 61 f. Dissertação (Programa de Pós-Graduação em Ciências da Saúde/CCBS) - Universidade Federal do Maranhão, São Luís, 2021.https://tedebc.ufma.br/jspui/handle/tede/tede/3538Mycobacterium tuberculosis (Mtb) is an intracellular pathogen, the causative agent of Tuberculosis (TB), which infects a large part of the world's population. About 90-95% of individuals infected with Mtb develop latent tuberculosis infection (LTBI), characterized by the formation of a structure called a granuloma, which maintains Mtb bacilli within a set of defense cells. The granuloma is considered hypoxic, and the response to hypoxia is regulated by the hypoxia-induced factor - HIF-1α, which has been associated with several infections, including bacterial ones. In addition to the hypoxia response, other mechanisms involved in active infection may contribute to the establishment of latent Mtb infection. The present study investigated how HIF-1α interferes in the innate immune response of individuals with active or latent infection. Therefore, patients with active pulmonary TB, before the start of treatment, individuals with latent tuberculosis infection (LTBI), who had PPD+ and IGRAs+ and healthy individuals were recruited. Expression of cytokines (IL-15, IL-18, IL-6 and TNF-α) and specific transcription factors (A20 and HIF-1α) that mediate mechanisms of the immune response in patients with active pulmonary TB, LTBI and healthy controls was performed. In addition, the activation of the vitamin D-dependent antimicrobial pathway, which is active by pro-inflammatory cytokines, was analyzed. IL-15 expression was decreased in LTBI subjects and active TB patients, while IL-18 expression was similar between LTBI subjects and healthy controls, both cytokines converge for vitamin D activation, which did not show a significant decrease. The expression of TNF-α and IL-6 were also lower in LTBI subjects. Regarding the transcription factors analyzed, there was a decrease in A20 and HIF-1α. The blockade of HIF-1α in PBMC of individuals with LTBI led to a decrease in the activation of phosphorylated NF-κB and an increase in the production of TNF-α, which may be determinant for the individual's latency condition. The decrease in cytokine production is relevant to keep the infection latent and influence the activation of the NF-κB signaling pathway. The results of this study demonstrate that LTBI is multifactorial, and several factors contribute to its establishment in the host.O Mycobacterium tuberculosis (Mtb) é um patógeno intracelular, agente causador da Tuberculose (TB), que infecta grande parte da população mundial. Cerca de 90-95% dos indivíduos infectados pelo Mtb, desenvolvem a infecção latente de tuberculose (ILTB), caracterizada pela formação de uma estrutura chamada de granuloma, que mantém os bacilos do Mtb no interior de um conjunto de células de defesa. O granuloma é considerado hipóxico, e a resposta a hipóxia é regulada pelo fator induzido por hipóxia – HIF-1α, que tem sido associado a diversas infecções, inclusive bacterianas. Além da resposta a hipoxia, outros mecanismos envolvidos na infecção ativa, podem contribuir para o estabelecimento da infecção latente por Mtb. O presente estudo buscou avaliar como o HIF-1α interfere na resposta imune inata de indivíduos com infecção ativa ou latente. Portanto, foram recrutados pacientes com TB pulmonar ativa, antes do início do tratamento, indivíduos com infecção latente de tuberculose (ILTB), que possuíram PPD+ e IGRAs+ e indivíduos saudáveis. Foi realizado expressão de citocinas (IL-15, IL-18, IL-6 e TNF-α) e fatores de transcrição específicos (A20 e HIF-1α) que medeiam mecanismos da resposta imunológica em pacientes com TB pulmonar ativa, indivíduos ILTB e controles saudáveis. Além disso, analisou-se a ativação da via antimicrobiana dependente da vitamina D, que é ativa por citocinas pró inflamatórias. A expressão de IL-15 foi diminuída em indivíduos ILTB e pacientes TB ativa, enquanto que a expressão de IL-18 foi semelhante entre indivíduos ILTB e controles saudáveis, ambas citocinas convergem para a ativação da vitamina D, que não demonstrou diminuição significativa. A expressão de TNF-α e IL-6 também foram menores em indivíduos ILTB. Em relação aos fatores de transcrição analisados, observou-se diminuição de A20 e HIF-1α. O bloqueio do HIF-1α nas PBMC de indivíduos com ILTB levou à diminuição da ativação do NF-κB fosforilado e ao aumento da produção de TNF-α, o que pode ser determinante para a condição de latência do indivíduo. A diminuição da produção de citocinas é relevante para manter a infecção latente e influenciar a ativação da via de sinalização do NF-κB. Os resultados deste estudo demonstram que a ILTB é multifatorial, e vários fatores contribuem para o seu estabelecimento no hospedeiro.Submitted by Jonathan Sousa de Almeida (jonathan.sousa@ufma.br) on 2022-04-28T14:27:58Z No. of bitstreams: 1 AlinedeOliveiraRezende.pdf: 1504431 bytes, checksum: 552167ca2f046bb0a0068a5d1d378a70 (MD5)Made available in DSpace on 2022-04-28T14:27:58Z (GMT). No. of bitstreams: 1 AlinedeOliveiraRezende.pdf: 1504431 bytes, checksum: 552167ca2f046bb0a0068a5d1d378a70 (MD5) Previous issue date: 2021-11-22CAPESapplication/pdfporUniversidade Federal do MaranhãoPROGRAMA DE PÓS-GRADUAÇÃO EM CIÊNCIAS DA SAÚDE/CCBSUFMABrasilDEPARTAMENTO DE MEDICINA II/CCBStuberculose;infecção latente de tuberculose;A20;fator induzido por hipóxia – HIF-1α;fator de necrose tumoral – TNF-α.tuberculosis;tatent tuberculosis infection;A20;hypoxia-induced factor – HIF-1α;tumor necrosis factor – TNF-α.Ciências da SaúdeAvaliação de genes relacionados à hipóxia associados à resposta imune inata de pacientes com tuberculose pulmonar ativa e latenteEvaluation of hypoxia-related genes associated with innate immune response in patients with active and latent pulmonary tuberculosisinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisinfo:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da UFMAinstname:Universidade Federal do Maranhão (UFMA)instacron:UFMAORIGINALAlinedeOliveiraRezende.pdfAlinedeOliveiraRezende.pdfapplication/pdf1504431http://tedebc.ufma.br:8080/bitstream/tede/3538/2/AlinedeOliveiraRezende.pdf552167ca2f046bb0a0068a5d1d378a70MD52LICENSElicense.txtlicense.txttext/plain; charset=utf-82255http://tedebc.ufma.br:8080/bitstream/tede/3538/1/license.txt97eeade1fce43278e63fe063657f8083MD51tede/35382023-05-15 15:47:29.417oai:tede2:tede/3538IExJQ0VOw4dBIERFIERJU1RSSUJVScOHw4NPIE7Dg08tRVhDTFVTSVZBCgpDb20gYSBhcHJlc2VudGHDp8OjbyBkZXN0YSBsaWNlbsOnYSxvIGF1dG9yIChlcykgb3UgbyB0aXR1bGFyIGRvcyBkaXJlaXRvcyBkZSBhdXRvciBjb25jZWRlIMOgIFVuaXZlcnNpZGFkZSBGZWRlcmFsIGRvIE1hcmFuaMOjbyAoVUZNQSkgbyBkaXJlaXRvIG7Do28tZXhjbHVzaXZvIGRlIHJlcHJvZHV6aXIsIHRyYWR1emlyIChjb25mb3JtZSBkZWZpbmlkbyBhYmFpeG8pLCBlL291IGRpc3RyaWJ1aXIgYSBzdWEgdGVzZSBvdSBkaXNzZXJ0YcOnw6NvIChpbmNsdWluZG8gbyByZXN1bW8pIHBvciB0b2RvIG8gbXVuZG8gbm8gZm9ybWF0byBpbXByZXNzbyBlIGVsZXRyw7RuaWNvIGUgZW0gcXVhbHF1ZXIgbWVpbywgaW5jbHVpbmRvIG9zIGZvcm1hdG9zIMOhdWRpbyBvdSB2w61kZW8uCgpWb2PDqiBjb25jb3JkYSBxdWUgYSBVRk1BIHBvZGUsIHNlbSBhbHRlcmFyIG8gY29udGXDumRvLCB0cmFuc3BvciBhIHN1YSB0ZXNlIG91IGRpc3NlcnRhw6fDo28gcGFyYSBxdWFscXVlciBtZWlvIG91IGZvcm1hdG8gcGFyYSBmaW5zIGRlIHByZXNlcnZhw6fDo28uCgpWb2PDqiB0YW1iw6ltIGNvbmNvcmRhIHF1ZSBhIFVGTUEgcG9kZSBtYW50ZXIgbWFpcyBkZSB1bWEgY8OzcGlhIGRlIHN1YSB0ZXNlIG91IGRpc3NlcnRhw6fDo28gcGFyYSBmaW5zIGRlIHNlZ3VyYW7Dp2EsIGJhY2stdXAgZSBwcmVzZXJ2YcOnw6NvLgoKVm9jw6ogZGVjbGFyYSBxdWUgYSBzdWEgdGVzZSBvdSBkaXNzZXJ0YcOnw6NvIMOpIG9yaWdpbmFsIGUgcXVlIHZvY8OqIHRlbSBvIHBvZGVyIGRlIGNvbmNlZGVyIG9zIGRpcmVpdG9zIGNvbnRpZG9zIG5lc3RhIGxpY2Vuw6dhLiBWb2PDqiB0YW1iw6ltIGRlY2xhcmEgcXVlIG8gZGVww7NzaXRvIGRhIHN1YSB0ZXNlIG91IGRpc3NlcnRhw6fDo28gbsOjbywgcXVlIHNlamEgZGUgc2V1IGNvbmhlY2ltZW50bywgaW5mcmluZ2UgZGlyZWl0b3MgYXV0b3JhaXMgZGUgbmluZ3XDqW0uCgpDYXNvIGEgc3VhIHRlc2Ugb3UgZGlzc2VydGHDp8OjbyBjb250ZW5oYSBtYXRlcmlhbCBxdWUgdm9jw6ogbsOjbyBwb3NzdWkgYSB0aXR1bGFyaWRhZGUgZG9zIGRpcmVpdG9zIGF1dG9yYWlzLCB2b2PDqiBkZWNsYXJhIHF1ZSBvYnRldmUgYSBwZXJtaXNzw6NvIGlycmVzdHJpdGEgZG8gZGV0ZW50b3IgZG9zIGRpcmVpdG9zIGF1dG9yYWlzIHBhcmEgY29uY2VkZXIgw6AgVUZNQSBvcyBkaXJlaXRvcyBhcHJlc2VudGFkb3MgbmVzdGEgbGljZW7Dp2EsIGUgcXVlIGVzc2UgbWF0ZXJpYWwgZGUgcHJvcHJpZWRhZGUgZGUgdGVyY2Vpcm9zIGVzdMOhIGNsYXJhbWVudGUgaWRlbnRpZmljYWRvIGUgcmVjb25oZWNpZG8gbm8gdGV4dG8gb3Ugbm8gY29udGXDumRvIGRhIHRlc2Ugb3UgZGlzc2VydGHDp8OjbyBvcmEgZGVwb3NpdGFkYS4KCkNBU08gQSBURVNFIE9VIERJU1NFUlRBw4fDg08gT1JBIERFUE9TSVRBREEgVEVOSEEgU0lETyBSRVNVTFRBRE8gREUgVU0gUEFUUk9Dw41OSU8gT1UgQVBPSU8gREUgVU1BIEFHw4pOQ0lBIERFIEZPTUVOVE8gT1UgT1VUUk8gT1JHQU5JU01PIFFVRSBOw4NPIFNFSkEgQSBVRk1BLCBWT0PDiiBERUNMQVJBIFFVRSBSRVNQRUlUT1UgVE9ET1MgRSBRVUFJU1FVRVIgRElSRUlUT1MgREUgUkVWSVPDg08gQ09NTyBUQU1Cw4lNIEFTIERFTUFJUyBPQlJJR0HDh8OVRVMgRVhJR0lEQVMgUE9SIENPTlRSQVRPIE9VIEFDT1JETy4KCkEgVUZNQSBzZSBjb21wcm9tZXRlIGEgaWRlbnRpZmljYXIgY2xhcmFtZW50ZSBvIHNldSBub21lIG91IG8ocykgbm9tZShzKSBkbyhzKSBkZXRlbnRvcihlcykgZG9zIGRpcmVpdG9zIGF1dG9yYWlzIGRhIHRlc2Ugb3UgZGlzc2VydGHDp8OjbywgZSBuw6NvIGZhcsOhIHF1YWxxdWVyIGFsdGVyYcOnw6NvLCBhbMOpbSBkYXF1ZWxhcyBjb25jZWRpZGFzIHBvciBlc3RhIGxpY2Vuw6dhLgoKRGVjbGFyYSB0YW1iw6ltIHF1ZSB0b2RhcyBhcyBhZmlsaWHDp8O1ZXMgY29ycG9yYXRpdmFzIG91IGluc3RpdHVjaW9uYWlzIGUgdG9kYXMgYXMgZm9udGVzIGRlIGFwb2lvIGZpbmFuY2Vpcm8gYW8gdHJhYmFsaG8gZXN0w6NvIGRldmlkYW1lbnRlIGNpdGFkYXMgb3UgbWVuY2lvbmFkYXMgZSBjZXJ0aWZpY2EgcXVlIG7Do28gaMOhIG5lbmh1bSBpbnRlcmVzc2UgY29tZXJjaWFsIG91IGFzc29jaWF0aXZvIHF1ZSByZXByZXNlbnRlIGNvbmZsaXRvIGRlIGludGVyZXNzZSBlbSBjb25leMOjbyBjb20gbyB0cmFiYWxobyBzdWJtZXRpZG8uCgoKCgoKCgo=Biblioteca Digital de Teses e Dissertaçõeshttps://tedebc.ufma.br/jspui/PUBhttp://tedebc.ufma.br:8080/oai/requestrepositorio@ufma.br||repositorio@ufma.bropendoar:21312023-05-15T18:47:29Biblioteca Digital de Teses e Dissertações da UFMA - Universidade Federal do Maranhão (UFMA)false |
dc.title.por.fl_str_mv |
Avaliação de genes relacionados à hipóxia associados à resposta imune inata de pacientes com tuberculose pulmonar ativa e latente |
dc.title.alternative.eng.fl_str_mv |
Evaluation of hypoxia-related genes associated with innate immune response in patients with active and latent pulmonary tuberculosis |
title |
Avaliação de genes relacionados à hipóxia associados à resposta imune inata de pacientes com tuberculose pulmonar ativa e latente |
spellingShingle |
Avaliação de genes relacionados à hipóxia associados à resposta imune inata de pacientes com tuberculose pulmonar ativa e latente REZENDE, Aline de Oliveira tuberculose; infecção latente de tuberculose; A20; fator induzido por hipóxia – HIF-1α; fator de necrose tumoral – TNF-α. tuberculosis; tatent tuberculosis infection; A20; hypoxia-induced factor – HIF-1α; tumor necrosis factor – TNF-α. Ciências da Saúde |
title_short |
Avaliação de genes relacionados à hipóxia associados à resposta imune inata de pacientes com tuberculose pulmonar ativa e latente |
title_full |
Avaliação de genes relacionados à hipóxia associados à resposta imune inata de pacientes com tuberculose pulmonar ativa e latente |
title_fullStr |
Avaliação de genes relacionados à hipóxia associados à resposta imune inata de pacientes com tuberculose pulmonar ativa e latente |
title_full_unstemmed |
Avaliação de genes relacionados à hipóxia associados à resposta imune inata de pacientes com tuberculose pulmonar ativa e latente |
title_sort |
Avaliação de genes relacionados à hipóxia associados à resposta imune inata de pacientes com tuberculose pulmonar ativa e latente |
author |
REZENDE, Aline de Oliveira |
author_facet |
REZENDE, Aline de Oliveira |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
SOUSA, Eduardo Martins de |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/4448263553675550 |
dc.contributor.advisor-co1.fl_str_mv |
PEREIRA, Paulo Vitor Soeiro |
dc.contributor.advisor-co1Lattes.fl_str_mv |
http://lattes.cnpq.br/7281767698416958 |
dc.contributor.referee1.fl_str_mv |
SOUSA, Eduardo Martins de |
dc.contributor.referee1Lattes.fl_str_mv |
http://lattes.cnpq.br/4448263553675550 |
dc.contributor.referee2.fl_str_mv |
SANTOS, Ana Paula Silva de Azevedo dos |
dc.contributor.referee2Lattes.fl_str_mv |
http://lattes.cnpq.br/8224124082144965 |
dc.contributor.referee3.fl_str_mv |
LIBERIO, Rosane Nassar Meireles Guerra |
dc.contributor.referee3Lattes.fl_str_mv |
http://lattes.cnpq.br/2316192786452127 |
dc.contributor.referee4.fl_str_mv |
COSTA, Adeliane Castro |
dc.contributor.referee4Lattes.fl_str_mv |
http://lattes.cnpq.br/9373163292240939 |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/2488628088138033 |
dc.contributor.author.fl_str_mv |
REZENDE, Aline de Oliveira |
contributor_str_mv |
SOUSA, Eduardo Martins de PEREIRA, Paulo Vitor Soeiro SOUSA, Eduardo Martins de SANTOS, Ana Paula Silva de Azevedo dos LIBERIO, Rosane Nassar Meireles Guerra COSTA, Adeliane Castro |
dc.subject.por.fl_str_mv |
tuberculose; infecção latente de tuberculose; A20; fator induzido por hipóxia – HIF-1α; fator de necrose tumoral – TNF-α. |
topic |
tuberculose; infecção latente de tuberculose; A20; fator induzido por hipóxia – HIF-1α; fator de necrose tumoral – TNF-α. tuberculosis; tatent tuberculosis infection; A20; hypoxia-induced factor – HIF-1α; tumor necrosis factor – TNF-α. Ciências da Saúde |
dc.subject.eng.fl_str_mv |
tuberculosis; tatent tuberculosis infection; A20; hypoxia-induced factor – HIF-1α; tumor necrosis factor – TNF-α. |
dc.subject.cnpq.fl_str_mv |
Ciências da Saúde |
description |
Mycobacterium tuberculosis (Mtb) is an intracellular pathogen, the causative agent of Tuberculosis (TB), which infects a large part of the world's population. About 90-95% of individuals infected with Mtb develop latent tuberculosis infection (LTBI), characterized by the formation of a structure called a granuloma, which maintains Mtb bacilli within a set of defense cells. The granuloma is considered hypoxic, and the response to hypoxia is regulated by the hypoxia-induced factor - HIF-1α, which has been associated with several infections, including bacterial ones. In addition to the hypoxia response, other mechanisms involved in active infection may contribute to the establishment of latent Mtb infection. The present study investigated how HIF-1α interferes in the innate immune response of individuals with active or latent infection. Therefore, patients with active pulmonary TB, before the start of treatment, individuals with latent tuberculosis infection (LTBI), who had PPD+ and IGRAs+ and healthy individuals were recruited. Expression of cytokines (IL-15, IL-18, IL-6 and TNF-α) and specific transcription factors (A20 and HIF-1α) that mediate mechanisms of the immune response in patients with active pulmonary TB, LTBI and healthy controls was performed. In addition, the activation of the vitamin D-dependent antimicrobial pathway, which is active by pro-inflammatory cytokines, was analyzed. IL-15 expression was decreased in LTBI subjects and active TB patients, while IL-18 expression was similar between LTBI subjects and healthy controls, both cytokines converge for vitamin D activation, which did not show a significant decrease. The expression of TNF-α and IL-6 were also lower in LTBI subjects. Regarding the transcription factors analyzed, there was a decrease in A20 and HIF-1α. The blockade of HIF-1α in PBMC of individuals with LTBI led to a decrease in the activation of phosphorylated NF-κB and an increase in the production of TNF-α, which may be determinant for the individual's latency condition. The decrease in cytokine production is relevant to keep the infection latent and influence the activation of the NF-κB signaling pathway. The results of this study demonstrate that LTBI is multifactorial, and several factors contribute to its establishment in the host. |
publishDate |
2021 |
dc.date.issued.fl_str_mv |
2021-11-22 |
dc.date.accessioned.fl_str_mv |
2022-04-28T14:27:58Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
format |
masterThesis |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
REZENDE, Aline de Oliveira. Avaliação de genes relacionados à hipóxia associados à resposta imune inata de pacientes com tuberculose pulmonar ativa e latente. 2021. 61 f. Dissertação (Programa de Pós-Graduação em Ciências da Saúde/CCBS) - Universidade Federal do Maranhão, São Luís, 2021. |
dc.identifier.uri.fl_str_mv |
https://tedebc.ufma.br/jspui/handle/tede/tede/3538 |
identifier_str_mv |
REZENDE, Aline de Oliveira. Avaliação de genes relacionados à hipóxia associados à resposta imune inata de pacientes com tuberculose pulmonar ativa e latente. 2021. 61 f. Dissertação (Programa de Pós-Graduação em Ciências da Saúde/CCBS) - Universidade Federal do Maranhão, São Luís, 2021. |
url |
https://tedebc.ufma.br/jspui/handle/tede/tede/3538 |
dc.language.iso.fl_str_mv |
por |
language |
por |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
dc.publisher.none.fl_str_mv |
Universidade Federal do Maranhão |
dc.publisher.program.fl_str_mv |
PROGRAMA DE PÓS-GRADUAÇÃO EM CIÊNCIAS DA SAÚDE/CCBS |
dc.publisher.initials.fl_str_mv |
UFMA |
dc.publisher.country.fl_str_mv |
Brasil |
dc.publisher.department.fl_str_mv |
DEPARTAMENTO DE MEDICINA II/CCBS |
publisher.none.fl_str_mv |
Universidade Federal do Maranhão |
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