The Metabolic Sensor GPR43 Receptor Plays a Role in the Control of Klebsiella Pneumoniae Infection in the Lung
Autor(a) principal: | |
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Data de Publicação: | 2018 |
Outros Autores: | , , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNIFESP |
Texto Completo: | https://repositorio.unifesp.br/handle/11600/54123 http://dx.doi.org/10.3389/fimmu.2018.00142 |
Resumo: | Pneumonia is one of the leading causes of death and mortality worldwide. The inflammatory responses that follow respiratory infections are protective leading to pathogen clearance but can also be deleterious if unregulated. The microbiota is known to be an important protective barrier against infections, mediating both direct inhibitory effects against the potential pathogen and also regulating the immune responses contributing to a proper clearance of the pathogen and return to homeostasis. GPR43 is one receptor for acetate, a microbiota metabolite shown to induce and to regulate important immune functions. Here, we addressed the role of GPR43 signaling during pulmonary bacterial infections. We have shown for the first time that the absence of GPR43 leads to increased susceptibility to Klebsiella pneumoniae infection, which was associated to both uncontrolled proliferation of bacteria and to increased inflammatory response. Mechanistically, we showed that GPR43 expression especially in neutrophils and alveolar macrophages is important for bacterial phagocytosis and killing. In addition, treatment with the GPR43 ligand, acetate, is protective during bacterial lung infection. This was associated to reduction in the number of bacteria in the airways and to the control of the inflammatory responses. Altogether, GPR43 plays an important role in the "gut-lung axis" as a sensor of the host gut microbiota activity through acetate binding promoting a proper immune response in the lungs. |
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Galvao, IzabelaTavares, Luciana P.Correa, Renan O.Fachi, Jose LuisRocha, Vitor MeloRungue, MarcelaGarcia, Cristiana C.Cassali, GeovanniFerreira, Caroline M. [UNIFESP]Martins, Flaviano S.Oliveira, Sergio C.Mackay, Charles R.Teixeira, Mauro M.Vinolo, Marco Aurelio R.Vieira, Angelica T.2020-07-08T13:09:40Z2020-07-08T13:09:40Z2018Frontiers In Immunology. Lausanne, v. 9, p. -, 2018.1664-3224https://repositorio.unifesp.br/handle/11600/54123http://dx.doi.org/10.3389/fimmu.2018.00142WOS000425521100001.pdf10.3389/fimmu.2018.00142WOS:000425521100001Pneumonia is one of the leading causes of death and mortality worldwide. The inflammatory responses that follow respiratory infections are protective leading to pathogen clearance but can also be deleterious if unregulated. The microbiota is known to be an important protective barrier against infections, mediating both direct inhibitory effects against the potential pathogen and also regulating the immune responses contributing to a proper clearance of the pathogen and return to homeostasis. GPR43 is one receptor for acetate, a microbiota metabolite shown to induce and to regulate important immune functions. Here, we addressed the role of GPR43 signaling during pulmonary bacterial infections. We have shown for the first time that the absence of GPR43 leads to increased susceptibility to Klebsiella pneumoniae infection, which was associated to both uncontrolled proliferation of bacteria and to increased inflammatory response. Mechanistically, we showed that GPR43 expression especially in neutrophils and alveolar macrophages is important for bacterial phagocytosis and killing. In addition, treatment with the GPR43 ligand, acetate, is protective during bacterial lung infection. This was associated to reduction in the number of bacteria in the airways and to the control of the inflammatory responses. Altogether, GPR43 plays an important role in the "gut-lung axis" as a sensor of the host gut microbiota activity through acetate binding promoting a proper immune response in the lungs.Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)Coordenacnao de aperfeicoamento de pessoal de Nivel Superior (CAPES)Rede Mineira de Imunobiologicos from the Fundacao de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG)Australian National Health and Medical Research Council (NHMRC)Pro-reitoria de Pesquisa, Universidade Federal de Minas Gerais (PRPQ-UFMG)Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)Fundacao de Desenvolvimento da Unicamp (Funcamp)Univ Fed Minas Gerais, Inst Biol Sci, Dept Biochem & Immunol, Belo Horizonte, MG, BrazilUniv Estadual Campinas, Inst Biol, Dept Genet Evolut & Bioagents, Campinas, SP, BrazilFiocruz MS, Inst Oswaldo Cruz, Lab Resp Viruses & Measles, Rio De Janeiro, BrazilUniv Fed Minas Gerais, Inst Biol Sci, Dept Gen Pathol, Belo Horizonte, MG, BrazilUniv Fed Sao Paulo, Inst Environm Chem & Pharmaceut Sci, Dept Pharmaceut Sci, Diadema, BrazilUniv Fed Minas Gerais, Inst Biol Sci, Dept Microbiol, Belo Horizonte, MG, BrazilMonash Univ, Dept Immunol, Melborne, Vic, AustraliaUniv Fed Sao Paulo, Inst Environm Chem & Pharmaceut Sci, Dept Pharmaceut Sci, Diadema, BrazilFAPEMIG: RED-00140-16PRPQ-UFMG: 23853FAPESP:12/10653-9, 14/22909-3Web of Science-engFrontiers Media SaFrontiers In Immunologylung infectionGPR43inflammationmicrobiotashort-chain fatty acidspneumoniaThe Metabolic Sensor GPR43 Receptor Plays a Role in the Control of Klebsiella Pneumoniae Infection in the Lunginfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleLausanne9info:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESPORIGINALWOS000425521100001.pdfapplication/pdf1638791${dspace.ui.url}/bitstream/11600/54123/1/WOS000425521100001.pdfcc48a05ea3c7bcc8a19c20f30768813aMD51open accessTEXTWOS000425521100001.pdf.txtWOS000425521100001.pdf.txtExtracted texttext/plain52336${dspace.ui.url}/bitstream/11600/54123/8/WOS000425521100001.pdf.txt36a667ea90ea1570a768a90e8aa43ac8MD58open accessTHUMBNAILWOS000425521100001.pdf.jpgWOS000425521100001.pdf.jpgIM Thumbnailimage/jpeg7404${dspace.ui.url}/bitstream/11600/54123/10/WOS000425521100001.pdf.jpgd0dda19c3be22601a7aa598dde2a281dMD510open access11600/541232023-06-05 19:27:14.32open accessoai:repositorio.unifesp.br:11600/54123Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestopendoar:34652023-06-05T22:27:14Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
dc.title.en.fl_str_mv |
The Metabolic Sensor GPR43 Receptor Plays a Role in the Control of Klebsiella Pneumoniae Infection in the Lung |
title |
The Metabolic Sensor GPR43 Receptor Plays a Role in the Control of Klebsiella Pneumoniae Infection in the Lung |
spellingShingle |
The Metabolic Sensor GPR43 Receptor Plays a Role in the Control of Klebsiella Pneumoniae Infection in the Lung Galvao, Izabela lung infection GPR43 inflammation microbiota short-chain fatty acids pneumonia |
title_short |
The Metabolic Sensor GPR43 Receptor Plays a Role in the Control of Klebsiella Pneumoniae Infection in the Lung |
title_full |
The Metabolic Sensor GPR43 Receptor Plays a Role in the Control of Klebsiella Pneumoniae Infection in the Lung |
title_fullStr |
The Metabolic Sensor GPR43 Receptor Plays a Role in the Control of Klebsiella Pneumoniae Infection in the Lung |
title_full_unstemmed |
The Metabolic Sensor GPR43 Receptor Plays a Role in the Control of Klebsiella Pneumoniae Infection in the Lung |
title_sort |
The Metabolic Sensor GPR43 Receptor Plays a Role in the Control of Klebsiella Pneumoniae Infection in the Lung |
author |
Galvao, Izabela |
author_facet |
Galvao, Izabela Tavares, Luciana P. Correa, Renan O. Fachi, Jose Luis Rocha, Vitor Melo Rungue, Marcela Garcia, Cristiana C. Cassali, Geovanni Ferreira, Caroline M. [UNIFESP] Martins, Flaviano S. Oliveira, Sergio C. Mackay, Charles R. Teixeira, Mauro M. Vinolo, Marco Aurelio R. Vieira, Angelica T. |
author_role |
author |
author2 |
Tavares, Luciana P. Correa, Renan O. Fachi, Jose Luis Rocha, Vitor Melo Rungue, Marcela Garcia, Cristiana C. Cassali, Geovanni Ferreira, Caroline M. [UNIFESP] Martins, Flaviano S. Oliveira, Sergio C. Mackay, Charles R. Teixeira, Mauro M. Vinolo, Marco Aurelio R. Vieira, Angelica T. |
author2_role |
author author author author author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Galvao, Izabela Tavares, Luciana P. Correa, Renan O. Fachi, Jose Luis Rocha, Vitor Melo Rungue, Marcela Garcia, Cristiana C. Cassali, Geovanni Ferreira, Caroline M. [UNIFESP] Martins, Flaviano S. Oliveira, Sergio C. Mackay, Charles R. Teixeira, Mauro M. Vinolo, Marco Aurelio R. Vieira, Angelica T. |
dc.subject.eng.fl_str_mv |
lung infection GPR43 inflammation microbiota short-chain fatty acids pneumonia |
topic |
lung infection GPR43 inflammation microbiota short-chain fatty acids pneumonia |
description |
Pneumonia is one of the leading causes of death and mortality worldwide. The inflammatory responses that follow respiratory infections are protective leading to pathogen clearance but can also be deleterious if unregulated. The microbiota is known to be an important protective barrier against infections, mediating both direct inhibitory effects against the potential pathogen and also regulating the immune responses contributing to a proper clearance of the pathogen and return to homeostasis. GPR43 is one receptor for acetate, a microbiota metabolite shown to induce and to regulate important immune functions. Here, we addressed the role of GPR43 signaling during pulmonary bacterial infections. We have shown for the first time that the absence of GPR43 leads to increased susceptibility to Klebsiella pneumoniae infection, which was associated to both uncontrolled proliferation of bacteria and to increased inflammatory response. Mechanistically, we showed that GPR43 expression especially in neutrophils and alveolar macrophages is important for bacterial phagocytosis and killing. In addition, treatment with the GPR43 ligand, acetate, is protective during bacterial lung infection. This was associated to reduction in the number of bacteria in the airways and to the control of the inflammatory responses. Altogether, GPR43 plays an important role in the "gut-lung axis" as a sensor of the host gut microbiota activity through acetate binding promoting a proper immune response in the lungs. |
publishDate |
2018 |
dc.date.issued.fl_str_mv |
2018 |
dc.date.accessioned.fl_str_mv |
2020-07-08T13:09:40Z |
dc.date.available.fl_str_mv |
2020-07-08T13:09:40Z |
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info:eu-repo/semantics/publishedVersion |
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article |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
Frontiers In Immunology. Lausanne, v. 9, p. -, 2018. |
dc.identifier.uri.fl_str_mv |
https://repositorio.unifesp.br/handle/11600/54123 http://dx.doi.org/10.3389/fimmu.2018.00142 |
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1664-3224 |
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WOS000425521100001.pdf |
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10.3389/fimmu.2018.00142 |
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WOS:000425521100001 |
identifier_str_mv |
Frontiers In Immunology. Lausanne, v. 9, p. -, 2018. 1664-3224 WOS000425521100001.pdf 10.3389/fimmu.2018.00142 WOS:000425521100001 |
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https://repositorio.unifesp.br/handle/11600/54123 http://dx.doi.org/10.3389/fimmu.2018.00142 |
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Frontiers Media Sa |
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Frontiers Media Sa |
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