An?lise do papel dos ?cidos graxos de cadeia curta nas infec??es causadas por v?rus respirat?rios

Autor: Fernandes, Krist Helen Antunes
Přispěvatelé: Souza, Ana Paula Duarte de, Vinolo, Marco Aur?lio Ramirez
Jazyk: portugalština
Rok vydání: 2021
Předmět:
Zdroj: Biblioteca Digital de Teses e Dissertações da PUC_RS
Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS)
instacron:PUC_RS
Popis: Os ?cidos graxos de cadeia curta (AGCCs) s?o os principais metab?litos resultantes da fermenta??o dos prebi?ticos pelas bact?rias intestinais. Estes exercem diversas fun??es fisiol?gicas, incluindo modula??o do sistema imune, atenuando quadros inflamat?rio. O v?rus sincicial respirat?rio (VSR) e o rinov?rus (HRV) s?o v?rus ub?quos no ambiente e predominantes associados ? infec??o do trato respirat?rio especialmente em crian?as. Atualmente n?o h? vacina dispon?vel e os m?todos terap?uticos para atenuar a gravidade da doen?a causada por esses v?rus s?o limitados. Alternativas naturais, como o uso de prebi?ticos, fibras sol?veis alimentares, t?m sido estudadas para prevenir doen?as respirat?rias. Baseando-se nisso, nossa hip?tese ? que os ?cidos graxos de cadeia curta, pode estar associado ? menor severidade doen?a causada por VSR e HRV, modulando a resposta aos v?rus. Assim esse trabalho teve como objetivo principal avaliar os efeitos dos AGCCs sobre a infec??o causada pelos v?rus VSR e HRV. No primeiro estudo identificamos que a dieta rica em fibras sol?veis aumenta os n?veis de acetato protegendo contra a infec??o causada pelo VSR. O efeito protetor conferido pelo acetato foi em decorr?ncia ao aumento da produ??o IFN-? nos pulm?es, e esse mecanismo ? dependendo do receptor GPR43 e IFNAR. No segundo estudo observamos que os n?veis de acetato nas fezes de lactentes com bronquiolite por VSR eram diretamente associados com a melhora de par?metros de severidade da doen?a. O tratamento com AGCCs ex vivo das c?lulas obtidas do lavado nasal desses pacientes reduziu a carga viral, e o acetato foi capaz de aumentar a express?o de RIG-I, MAVS e ISG15. No terceiro estudo verificamos que o tratamento com acetato em c?lulas bronquiais epiteliais humanas protege contra a infec??o com HRV, reduzindo a presen?a do v?rus e aumentando a express?o g?nica de IFN-?, IFN-? e viperina. Em modelo experimental de infec??o por HRV, o tratamento com acetato aumentou a express?o de IFN-?, entretanto, ap?s 4 e 6 dias de infec??o e tratamento, reduziu a express?o de Muc5AC nos pulm?es. Juntos os resultados dos tr?s estudos demonstram um importante papel dos acidos graxos em especial o acetato, nas infec??es causadas por VSR e HRV, atrav?s da modula??o de IFN-? e seus ISGs e IFN-?. 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-? 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-?, IFN-? and viperin. In an experimental model of HRV infection, treatment with acetate increased the expression of IFN-?, 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-? and its ISGs and IFN-?. Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES
Databáze: OpenAIRE
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