Relevance of angiotensin-(1-7) and its receptor Mas in pneumonia caused by influenza virus and post-influenza pneumococcal infection
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Outros Autores: | , , , , , , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UFMG |
Texto Completo: | https://doi.org/10.1016/j.phrs.2020.105292 http://hdl.handle.net/1843/54167 |
Resumo: | Resolution failure of exacerbated inflammation triggered by Influenza A virus (IAV) prevents return of pulmonary homeostasis and survival, especially when associated with secondary pneumococcal infection. Therapeutic strategies based on pro-resolving molecules have great potential against acute inflammatory diseases. Angiotensin-(1–7) [Ang-(1–7)] is a pro-resolving mediator that acts on its Mas receptor (MasR) to promote resolution of inflammation. We investigated the effects of Ang-(1–7) and the role of MasR in the context of primary IAV infection and secondary pneumococcal infection and evaluated pulmonary inflammation, virus titers and bacteria counts, and pulmonary damage. Therapeutic treatment with Ang-(1–7) decreased neutrophil recruitment, lung injury, viral load and morbidity after a primary IAV infection. Ang-(1–7) induced apoptosis of neutrophils and efferocytosis of these cells by alveolar macrophages, but had no direct effect on IAV replication in vitro. MasR-deficient (MasR−/−) mice were highly susceptible to IAV infection, displaying uncontrolled inflammation, increased viral load and greater lethality rate, as compared to WT animals. Ang-(1–7) was not protective in MasR−/− mice. Interestingly, Ang-(1–7) given during a sublethal dose of IAV infection greatly reduced morbidity associated with a subsequent S. pneumoniae infection, as seen by decrease in the magnitude of neutrophil influx, number of bacteria in the blood leading to a lower lethality. Altogether, these results show that Ang-(1–7) is highly protective against severe primary IAV infection and protects against secondary bacterial infection of the lung. These effects are MasR-dependent. Mediators of resolution of inflammation, such as Ang-(1–7), should be considered for the treatment of pulmonary viral infections. |
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2023-05-30T13:11:28Z2023-05-30T13:11:28Z2021-01163112https://doi.org/10.1016/j.phrs.2020.1052921043-6618http://hdl.handle.net/1843/54167Resolution failure of exacerbated inflammation triggered by Influenza A virus (IAV) prevents return of pulmonary homeostasis and survival, especially when associated with secondary pneumococcal infection. Therapeutic strategies based on pro-resolving molecules have great potential against acute inflammatory diseases. Angiotensin-(1–7) [Ang-(1–7)] is a pro-resolving mediator that acts on its Mas receptor (MasR) to promote resolution of inflammation. We investigated the effects of Ang-(1–7) and the role of MasR in the context of primary IAV infection and secondary pneumococcal infection and evaluated pulmonary inflammation, virus titers and bacteria counts, and pulmonary damage. Therapeutic treatment with Ang-(1–7) decreased neutrophil recruitment, lung injury, viral load and morbidity after a primary IAV infection. Ang-(1–7) induced apoptosis of neutrophils and efferocytosis of these cells by alveolar macrophages, but had no direct effect on IAV replication in vitro. MasR-deficient (MasR−/−) mice were highly susceptible to IAV infection, displaying uncontrolled inflammation, increased viral load and greater lethality rate, as compared to WT animals. Ang-(1–7) was not protective in MasR−/− mice. Interestingly, Ang-(1–7) given during a sublethal dose of IAV infection greatly reduced morbidity associated with a subsequent S. pneumoniae infection, as seen by decrease in the magnitude of neutrophil influx, number of bacteria in the blood leading to a lower lethality. Altogether, these results show that Ang-(1–7) is highly protective against severe primary IAV infection and protects against secondary bacterial infection of the lung. These effects are MasR-dependent. Mediators of resolution of inflammation, such as Ang-(1–7), should be considered for the treatment of pulmonary viral infections.A falha na resolução da inflamação exacerbada desencadeada pelo vírus Influenza A (IAV) impede o retorno da homeostase pulmonar e a sobrevida, principalmente quando associada à infecção pneumocócica secundária. Estratégias terapêuticas baseadas em moléculas pró-resolutivas têm grande potencial contra doenças inflamatórias agudas. A angiotensina-(1–7) [Ang-(1–7)] é um mediador pró-resolução que atua em seu receptor Mas (MasR) para promover a resolução da inflamação. Investigamos os efeitos da Ang-(1–7) e o papel do MasR no contexto da infecção primária por IAV e infecção pneumocócica secundária e avaliamos a inflamação pulmonar, títulos de vírus e contagens de bactérias e danos pulmonares. O tratamento terapêutico com Ang-(1–7) diminuiu o recrutamento de neutrófilos, lesão pulmonar, carga viral e morbidade após uma infecção primária por IAV. A Ang-(1–7) induziu apoptose de neutrófilos e eferocitose dessas células por macrófagos alveolares, mas não teve efeito direto na replicação do IAV in vitro. Camundongos deficientes em MasR (MasR−/−) foram altamente suscetíveis à infecção por IAV, apresentando inflamação descontrolada, aumento da carga viral e maior taxa de letalidade, em comparação com animais WT. Ang-(1–7) não foi protetor em camundongos MasR−/−. Curiosamente, Ang-(1–7) administrado durante uma dose subletal de infecção por IAV reduziu muito a morbidade associada a uma infecção subseqüente por S. pneumoniae, conforme observado pela diminuição na magnitude do influxo de neutrófilos, número de bactérias no sangue levando a uma menor letalidade. No total, esses resultados mostram que Ang-(1–7) é altamente protetor contra infecção primária grave por IAV e protege contra infecção bacteriana secundária do pulmão. Esses efeitos são dependentes de MasR. Mediadores da resolução da inflamação, como Ang-(1–7), devem ser considerados para o tratamento de infecções virais pulmonares.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 SuperiorengUniversidade Federal de Minas GeraisUFMGBrasilFAR - DEPARTAMENTO DE ANÁLISES CLÍNICAS E TOXICOLÓGICASICB - DEPARTAMENTO DE MORFOLOGIAPharmacological ResearchOrthomyxoviridaeVírus da influenza AStreptococcus pneumoniaeAngiotensinasInflamaçãoInfecçõesInfluenza virusStreptococcus pneumoniaeAngiotensin-(1-7)InflammationResolutionInfectionRelevance of angiotensin-(1-7) and its receptor Mas in pneumonia caused by influenza virus and post-influenza pneumococcal infectioninfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttps://www.sciencedirect.com/science/article/pii/S1043661820316005Eliza Mathias MeloJuliana Lemos Del SartoJuliana Priscila Vago da SilvaLuciana Pádua TavaresFlávia Rago Glória GonçalvesAna Paula de Faria GonçalvesMarina Gomes MachadoIrene Aranda-PardosBruno Vinícius Santos ValiateGeovanni Dantas CassaliVanessa PinhoLirlândia Pires de SousaNoelia Alonso-GonzalezMaria José Campagnole dos SantosMichael BaderRobson Augusto Souza dos SantosAlexandre de Magalhães Vieira MachadoStephan LudwigMauro Martins Teixeiraapplication/pdfinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFMGinstname:Universidade Federal de Minas Gerais (UFMG)instacron:UFMGORIGINALRelevance of angiotensin-(1-7) and its receptor Mas in pneumonia caused by influenza virus and post-influenza pneumococcal infection.pdfRelevance of angiotensin-(1-7) and its receptor Mas in pneumonia caused by influenza virus and post-influenza pneumococcal infection.pdfapplication/pdf8210479https://repositorio.ufmg.br/bitstream/1843/54167/2/Relevance%20of%20angiotensin-%281-7%29%20and%20its%20receptor%20Mas%20in%20pneumonia%20caused%20by%20influenza%20virus%20and%20post-influenza%20pneumococcal%20infection.pdf51bd1fef13f064db1cc7d2aa7cd18745MD52LICENSELicense.txtLicense.txttext/plain; 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dc.title.pt_BR.fl_str_mv |
Relevance of angiotensin-(1-7) and its receptor Mas in pneumonia caused by influenza virus and post-influenza pneumococcal infection |
title |
Relevance of angiotensin-(1-7) and its receptor Mas in pneumonia caused by influenza virus and post-influenza pneumococcal infection |
spellingShingle |
Relevance of angiotensin-(1-7) and its receptor Mas in pneumonia caused by influenza virus and post-influenza pneumococcal infection Eliza Mathias Melo Influenza virus Streptococcus pneumoniae Angiotensin-(1-7) Inflammation Resolution Infection Orthomyxoviridae Vírus da influenza A Streptococcus pneumoniae Angiotensinas Inflamação Infecções |
title_short |
Relevance of angiotensin-(1-7) and its receptor Mas in pneumonia caused by influenza virus and post-influenza pneumococcal infection |
title_full |
Relevance of angiotensin-(1-7) and its receptor Mas in pneumonia caused by influenza virus and post-influenza pneumococcal infection |
title_fullStr |
Relevance of angiotensin-(1-7) and its receptor Mas in pneumonia caused by influenza virus and post-influenza pneumococcal infection |
title_full_unstemmed |
Relevance of angiotensin-(1-7) and its receptor Mas in pneumonia caused by influenza virus and post-influenza pneumococcal infection |
title_sort |
Relevance of angiotensin-(1-7) and its receptor Mas in pneumonia caused by influenza virus and post-influenza pneumococcal infection |
author |
Eliza Mathias Melo |
author_facet |
Eliza Mathias Melo Juliana Lemos Del Sarto Juliana Priscila Vago da Silva Luciana Pádua Tavares Flávia Rago Glória Gonçalves Ana Paula de Faria Gonçalves Marina Gomes Machado Irene Aranda-Pardos Bruno Vinícius Santos Valiate Geovanni Dantas Cassali Vanessa Pinho Lirlândia Pires de Sousa Noelia Alonso-Gonzalez Maria José Campagnole dos Santos Michael Bader Robson Augusto Souza dos Santos Alexandre de Magalhães Vieira Machado Stephan Ludwig Mauro Martins Teixeira |
author_role |
author |
author2 |
Juliana Lemos Del Sarto Juliana Priscila Vago da Silva Luciana Pádua Tavares Flávia Rago Glória Gonçalves Ana Paula de Faria Gonçalves Marina Gomes Machado Irene Aranda-Pardos Bruno Vinícius Santos Valiate Geovanni Dantas Cassali Vanessa Pinho Lirlândia Pires de Sousa Noelia Alonso-Gonzalez Maria José Campagnole dos Santos Michael Bader Robson Augusto Souza dos Santos Alexandre de Magalhães Vieira Machado Stephan Ludwig Mauro Martins Teixeira |
author2_role |
author author author author author author author author author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Eliza Mathias Melo Juliana Lemos Del Sarto Juliana Priscila Vago da Silva Luciana Pádua Tavares Flávia Rago Glória Gonçalves Ana Paula de Faria Gonçalves Marina Gomes Machado Irene Aranda-Pardos Bruno Vinícius Santos Valiate Geovanni Dantas Cassali Vanessa Pinho Lirlândia Pires de Sousa Noelia Alonso-Gonzalez Maria José Campagnole dos Santos Michael Bader Robson Augusto Souza dos Santos Alexandre de Magalhães Vieira Machado Stephan Ludwig Mauro Martins Teixeira |
dc.subject.por.fl_str_mv |
Influenza virus Streptococcus pneumoniae Angiotensin-(1-7) Inflammation Resolution Infection |
topic |
Influenza virus Streptococcus pneumoniae Angiotensin-(1-7) Inflammation Resolution Infection Orthomyxoviridae Vírus da influenza A Streptococcus pneumoniae Angiotensinas Inflamação Infecções |
dc.subject.other.pt_BR.fl_str_mv |
Orthomyxoviridae Vírus da influenza A Streptococcus pneumoniae Angiotensinas Inflamação Infecções |
description |
Resolution failure of exacerbated inflammation triggered by Influenza A virus (IAV) prevents return of pulmonary homeostasis and survival, especially when associated with secondary pneumococcal infection. Therapeutic strategies based on pro-resolving molecules have great potential against acute inflammatory diseases. Angiotensin-(1–7) [Ang-(1–7)] is a pro-resolving mediator that acts on its Mas receptor (MasR) to promote resolution of inflammation. We investigated the effects of Ang-(1–7) and the role of MasR in the context of primary IAV infection and secondary pneumococcal infection and evaluated pulmonary inflammation, virus titers and bacteria counts, and pulmonary damage. Therapeutic treatment with Ang-(1–7) decreased neutrophil recruitment, lung injury, viral load and morbidity after a primary IAV infection. Ang-(1–7) induced apoptosis of neutrophils and efferocytosis of these cells by alveolar macrophages, but had no direct effect on IAV replication in vitro. MasR-deficient (MasR−/−) mice were highly susceptible to IAV infection, displaying uncontrolled inflammation, increased viral load and greater lethality rate, as compared to WT animals. Ang-(1–7) was not protective in MasR−/− mice. Interestingly, Ang-(1–7) given during a sublethal dose of IAV infection greatly reduced morbidity associated with a subsequent S. pneumoniae infection, as seen by decrease in the magnitude of neutrophil influx, number of bacteria in the blood leading to a lower lethality. Altogether, these results show that Ang-(1–7) is highly protective against severe primary IAV infection and protects against secondary bacterial infection of the lung. These effects are MasR-dependent. Mediators of resolution of inflammation, such as Ang-(1–7), should be considered for the treatment of pulmonary viral infections. |
publishDate |
2021 |
dc.date.issued.fl_str_mv |
2021-01 |
dc.date.accessioned.fl_str_mv |
2023-05-30T13:11:28Z |
dc.date.available.fl_str_mv |
2023-05-30T13:11:28Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/1843/54167 |
dc.identifier.doi.pt_BR.fl_str_mv |
https://doi.org/10.1016/j.phrs.2020.105292 |
dc.identifier.issn.pt_BR.fl_str_mv |
1043-6618 |
url |
https://doi.org/10.1016/j.phrs.2020.105292 http://hdl.handle.net/1843/54167 |
identifier_str_mv |
1043-6618 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
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Pharmacological Research |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
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Universidade Federal de Minas Gerais |
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UFMG |
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Brasil |
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FAR - DEPARTAMENTO DE ANÁLISES CLÍNICAS E TOXICOLÓGICAS ICB - DEPARTAMENTO DE MORFOLOGIA |
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Universidade Federal de Minas Gerais |
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