Análise do papel dos ácidos graxos de cadeia curta nas infecções causadas por vírus respiratórios
Autor(a) principal: | |
---|---|
Data de Publicação: | 2021 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Biblioteca Digital de Teses e Dissertações da PUC_RS |
Texto Completo: | http://tede2.pucrs.br/tede2/handle/tede/9940 |
Resumo: | Short-chain fatty acids (SCFAs) are the main metabolites resulting from the fermentation of prebiotics by intestinal bacteria. These exert several physiological functions, including modulation of the immune system, attenuating inflammatory conditions. Respiratory syncytial virus (RSV) and rhinovirus (HRV) are ubiquitous viruses in the environment and prevalent associated with respiratory tract infection, especially in children. There is currently no vaccine available and therapeutic methods to mitigate the severity of the disease caused by these viruses are limited. Natural alternatives, such as the use of prebiotics, soluble dietary fibers, have been studied to prevent respiratory diseases. Based on this, our hypothesis is that short-chain fatty acids may be associated with less severe disease caused by RSV and HRV, modulating the response to viruses. Thus, this work had as main objective to evaluate the effects of SCFAs on the infection caused by the RSV and HRV viruses. In the first study we identified that the diet rich in soluble fibers increases the levels of acetate protecting against infection caused by RSV. The protective effect conferred by acetate was due to the increase in the production of IFN-β in the lungs, and this mechanism depends on the GPR43 and IFNAR receptors. In the second study, we observed that the levels of acetate in the feces of infants with bronchiolitis caused by RSV were directly associated with the improvement of disease severity parameters. Ex vivo treatment with SCFAs of cells obtained from the nasal wash of these patients reduced viral load, and acetate was able to increase the expression of RIG-I, MAVS and ISG15. In the third study, we found that treatment with acetate in human epithelial bronchial cells protects against infection with HRV, reducing the presence of the virus and increasing the gene expression of IFN-β, IFN-λ and viperin. In an experimental model of HRV infection, treatment with acetate increased the expression of IFN-λ, however, after 4 and 6 days of infection and treatment, it reduced the expression of Muc5AC in the lungs. Together, the results of the three studies demonstrate an important role of fatty acids, especially acetate, in infections caused by RSV and HRV, through the modulation of IFN-β and its ISGs and IFN-λ. |
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Souza, Ana Paula Duarte dehttp://lattes.cnpq.br/7065225247536877Vinolo, Marco Aurélio Ramirezhttp://lattes.cnpq.br/6165339279159262http://lattes.cnpq.br/4943020602531256Fernandes, Krist Helen Antunes2021-10-28T12:54:59Z2021-02-24http://tede2.pucrs.br/tede2/handle/tede/9940Short-chain fatty acids (SCFAs) are the main metabolites resulting from the fermentation of prebiotics by intestinal bacteria. These exert several physiological functions, including modulation of the immune system, attenuating inflammatory conditions. Respiratory syncytial virus (RSV) and rhinovirus (HRV) are ubiquitous viruses in the environment and prevalent associated with respiratory tract infection, especially in children. There is currently no vaccine available and therapeutic methods to mitigate the severity of the disease caused by these viruses are limited. Natural alternatives, such as the use of prebiotics, soluble dietary fibers, have been studied to prevent respiratory diseases. Based on this, our hypothesis is that short-chain fatty acids may be associated with less severe disease caused by RSV and HRV, modulating the response to viruses. Thus, this work had as main objective to evaluate the effects of SCFAs on the infection caused by the RSV and HRV viruses. In the first study we identified that the diet rich in soluble fibers increases the levels of acetate protecting against infection caused by RSV. The protective effect conferred by acetate was due to the increase in the production of IFN-β in the lungs, and this mechanism depends on the GPR43 and IFNAR receptors. In the second study, we observed that the levels of acetate in the feces of infants with bronchiolitis caused by RSV were directly associated with the improvement of disease severity parameters. Ex vivo treatment with SCFAs of cells obtained from the nasal wash of these patients reduced viral load, and acetate was able to increase the expression of RIG-I, MAVS and ISG15. In the third study, we found that treatment with acetate in human epithelial bronchial cells protects against infection with HRV, reducing the presence of the virus and increasing the gene expression of IFN-β, IFN-λ and viperin. In an experimental model of HRV infection, treatment with acetate increased the expression of IFN-λ, however, after 4 and 6 days of infection and treatment, it reduced the expression of Muc5AC in the lungs. Together, the results of the three studies demonstrate an important role of fatty acids, especially acetate, in infections caused by RSV and HRV, through the modulation of IFN-β and its ISGs and IFN-λ.Os ácidos graxos de cadeia curta (AGCCs) são os principais metabólitos resultantes da fermentação dos prebióticos pelas bactérias intestinais. Estes exercem diversas funções fisiológicas, incluindo modulação do sistema imune, atenuando quadros inflamatório. O vírus sincicial respiratório (VSR) e o rinovírus (HRV) são vírus ubíquos no ambiente e predominantes associados à infecção do trato respiratório especialmente em crianças. Atualmente não há vacina disponível e os métodos terapêuticos para atenuar a gravidade da doença causada por esses vírus são limitados. Alternativas naturais, como o uso de prebióticos, fibras solúveis alimentares, têm sido estudadas para prevenir doenças respiratórias. Baseando-se nisso, nossa hipótese é que os ácidos graxos de cadeia curta, pode estar associado à menor severidade doença causada por VSR e HRV, modulando a resposta aos vírus. Assim esse trabalho teve como objetivo principal avaliar os efeitos dos AGCCs sobre a infecção causada pelos vírus VSR e HRV. No primeiro estudo identificamos que a dieta rica em fibras solúveis aumenta os níveis de acetato protegendo contra a infecção causada pelo VSR. O efeito protetor conferido pelo acetato foi em decorrência ao aumento da produção IFN-β nos pulmões, e esse mecanismo é dependendo do receptor GPR43 e IFNAR. No segundo estudo observamos que os níveis de acetato nas fezes de lactentes com bronquiolite por VSR eram diretamente associados com a melhora de parâmetros de severidade da doença. O tratamento com AGCCs ex vivo das células obtidas do lavado nasal desses pacientes reduziu a carga viral, e o acetato foi capaz de aumentar a expressão de RIG-I, MAVS e ISG15. No terceiro estudo verificamos que o tratamento com acetato em células bronquiais epiteliais humanas protege contra a infecção com HRV, reduzindo a presença do vírus e aumentando a expressão gênica de IFN-β, IFN-λ e viperina. Em modelo experimental de infecção por HRV, o tratamento com acetato aumentou a expressão de IFN-λ, entretanto, após 4 e 6 dias de infecção e tratamento, reduziu a expressão de Muc5AC nos pulmões. Juntos os resultados dos três estudos demonstram um importante papel dos acidos graxos em especial o acetato, nas infecções causadas por VSR e HRV, através da modulação de IFN-β e seus ISGs e IFN-λ.Submitted by PPG Pediatria e Saúde da Criança (pediatria-pg@pucrs.br) on 2021-10-26T19:00:38Z No. of bitstreams: 1 Tese Krist Versão final 2610.pdf: 11428851 bytes, checksum: 69fbc045b9095684e1736146d6c36ba8 (MD5)Approved for entry into archive by Caroline Xavier (caroline.xavier@pucrs.br) on 2021-10-28T12:52:20Z (GMT) No. of bitstreams: 1 Tese Krist Versão final 2610.pdf: 11428851 bytes, checksum: 69fbc045b9095684e1736146d6c36ba8 (MD5)Made available in DSpace on 2021-10-28T12:54:59Z (GMT). No. of bitstreams: 1 Tese Krist Versão final 2610.pdf: 11428851 bytes, checksum: 69fbc045b9095684e1736146d6c36ba8 (MD5) Previous issue date: 2021-02-24Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESapplication/pdfhttp://tede2.pucrs.br:80/tede2/retrieve/182485/TES_KRIST_HELEN_ANTUNES_FERNANDES_CONFIDENCIAL.pdf.jpgporPontifícia Universidade Católica do Rio Grande do SulPrograma de Pós-Graduação em Medicina/Pediatria e Saúde da CriançaPUCRSBrasilEscola de MedicinaVirus Sincicial RespiratórioÁcidos Graxos de Cadeia CurtaRespiratory Syncytial VirusShort Chain Fatty AcidsCIENCIAS DA SAUDE::MEDICINAMEDICINA::SAUDE MATERNO-INFANTILAnálise do papel dos ácidos graxos de cadeia curta nas infecções causadas por vírus respiratóriosinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisTrabalho será publicado como artigo ou livro60 meses28/10/2026557290555552975733500500500600600-224747486637135387-969369452308786627-80674179539253457523590462550136975366info:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da PUC_RSinstname:Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS)instacron:PUC_RSTHUMBNAILTES_KRIST_HELEN_ANTUNES_FERNANDES_CONFIDENCIAL.pdf.jpgTES_KRIST_HELEN_ANTUNES_FERNANDES_CONFIDENCIAL.pdf.jpgimage/jpeg4119http://tede2.pucrs.br/tede2/bitstream/tede/9940/4/TES_KRIST_HELEN_ANTUNES_FERNANDES_CONFIDENCIAL.pdf.jpg47dd2b106fbea79ad1e9cee7f73b86a8MD54TEXTTES_KRIST_HELEN_ANTUNES_FERNANDES_CONFIDENCIAL.pdf.txtTES_KRIST_HELEN_ANTUNES_FERNANDES_CONFIDENCIAL.pdf.txttext/plain2032http://tede2.pucrs.br/tede2/bitstream/tede/9940/3/TES_KRIST_HELEN_ANTUNES_FERNANDES_CONFIDENCIAL.pdf.txt095be1e76863bff21efe303f4b467014MD53ORIGINALTES_KRIST_HELEN_ANTUNES_FERNANDES_CONFIDENCIAL.pdfTES_KRIST_HELEN_ANTUNES_FERNANDES_CONFIDENCIAL.pdfapplication/pdf550589http://tede2.pucrs.br/tede2/bitstream/tede/9940/2/TES_KRIST_HELEN_ANTUNES_FERNANDES_CONFIDENCIAL.pdfad9be89008d744732e1da6fd232eda5eMD52LICENSElicense.txtlicense.txttext/plain; charset=utf-8590http://tede2.pucrs.br/tede2/bitstream/tede/9940/1/license.txt220e11f2d3ba5354f917c7035aadef24MD51tede/99402021-10-28 13:00:24.381oai:tede2.pucrs.br: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Biblioteca Digital de Teses e Dissertaçõeshttp://tede2.pucrs.br/tede2/PRIhttps://tede2.pucrs.br/oai/requestbiblioteca.central@pucrs.br||opendoar:2021-10-28T15:00:24Biblioteca Digital de Teses e Dissertações da PUC_RS - Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS)false |
dc.title.por.fl_str_mv |
Análise do papel dos ácidos graxos de cadeia curta nas infecções causadas por vírus respiratórios |
title |
Análise do papel dos ácidos graxos de cadeia curta nas infecções causadas por vírus respiratórios |
spellingShingle |
Análise do papel dos ácidos graxos de cadeia curta nas infecções causadas por vírus respiratórios Fernandes, Krist Helen Antunes Virus Sincicial Respiratório Ácidos Graxos de Cadeia Curta Respiratory Syncytial Virus Short Chain Fatty Acids CIENCIAS DA SAUDE::MEDICINA MEDICINA::SAUDE MATERNO-INFANTIL |
title_short |
Análise do papel dos ácidos graxos de cadeia curta nas infecções causadas por vírus respiratórios |
title_full |
Análise do papel dos ácidos graxos de cadeia curta nas infecções causadas por vírus respiratórios |
title_fullStr |
Análise do papel dos ácidos graxos de cadeia curta nas infecções causadas por vírus respiratórios |
title_full_unstemmed |
Análise do papel dos ácidos graxos de cadeia curta nas infecções causadas por vírus respiratórios |
title_sort |
Análise do papel dos ácidos graxos de cadeia curta nas infecções causadas por vírus respiratórios |
author |
Fernandes, Krist Helen Antunes |
author_facet |
Fernandes, Krist Helen Antunes |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Souza, Ana Paula Duarte de |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/7065225247536877 |
dc.contributor.advisor-co1.fl_str_mv |
Vinolo, Marco Aurélio Ramirez |
dc.contributor.advisor-co1Lattes.fl_str_mv |
http://lattes.cnpq.br/6165339279159262 |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/4943020602531256 |
dc.contributor.author.fl_str_mv |
Fernandes, Krist Helen Antunes |
contributor_str_mv |
Souza, Ana Paula Duarte de Vinolo, Marco Aurélio Ramirez |
dc.subject.por.fl_str_mv |
Virus Sincicial Respiratório Ácidos Graxos de Cadeia Curta |
topic |
Virus Sincicial Respiratório Ácidos Graxos de Cadeia Curta Respiratory Syncytial Virus Short Chain Fatty Acids CIENCIAS DA SAUDE::MEDICINA MEDICINA::SAUDE MATERNO-INFANTIL |
dc.subject.eng.fl_str_mv |
Respiratory Syncytial Virus Short Chain Fatty Acids |
dc.subject.cnpq.fl_str_mv |
CIENCIAS DA SAUDE::MEDICINA MEDICINA::SAUDE MATERNO-INFANTIL |
description |
Short-chain fatty acids (SCFAs) are the main metabolites resulting from the fermentation of prebiotics by intestinal bacteria. These exert several physiological functions, including modulation of the immune system, attenuating inflammatory conditions. Respiratory syncytial virus (RSV) and rhinovirus (HRV) are ubiquitous viruses in the environment and prevalent associated with respiratory tract infection, especially in children. There is currently no vaccine available and therapeutic methods to mitigate the severity of the disease caused by these viruses are limited. Natural alternatives, such as the use of prebiotics, soluble dietary fibers, have been studied to prevent respiratory diseases. Based on this, our hypothesis is that short-chain fatty acids may be associated with less severe disease caused by RSV and HRV, modulating the response to viruses. Thus, this work had as main objective to evaluate the effects of SCFAs on the infection caused by the RSV and HRV viruses. In the first study we identified that the diet rich in soluble fibers increases the levels of acetate protecting against infection caused by RSV. The protective effect conferred by acetate was due to the increase in the production of IFN-β in the lungs, and this mechanism depends on the GPR43 and IFNAR receptors. In the second study, we observed that the levels of acetate in the feces of infants with bronchiolitis caused by RSV were directly associated with the improvement of disease severity parameters. Ex vivo treatment with SCFAs of cells obtained from the nasal wash of these patients reduced viral load, and acetate was able to increase the expression of RIG-I, MAVS and ISG15. In the third study, we found that treatment with acetate in human epithelial bronchial cells protects against infection with HRV, reducing the presence of the virus and increasing the gene expression of IFN-β, IFN-λ and viperin. In an experimental model of HRV infection, treatment with acetate increased the expression of IFN-λ, however, after 4 and 6 days of infection and treatment, it reduced the expression of Muc5AC in the lungs. Together, the results of the three studies demonstrate an important role of fatty acids, especially acetate, in infections caused by RSV and HRV, through the modulation of IFN-β and its ISGs and IFN-λ. |
publishDate |
2021 |
dc.date.accessioned.fl_str_mv |
2021-10-28T12:54:59Z |
dc.date.issued.fl_str_mv |
2021-02-24 |
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por |
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Pontifícia Universidade Católica do Rio Grande do Sul |
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Programa de Pós-Graduação em Medicina/Pediatria e Saúde da Criança |
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Brasil |
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