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: | http://dx.doi.org/10.3389/fimmu.2018.00142 https://repositorio.unifesp.br/handle/11600/54123 |
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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The Metabolic Sensor GPR43 Receptor Plays a Role in the Control of Klebsiella Pneumoniae Infection in the Lunglung infectionGPR43inflammationmicrobiotashort-chain fatty acidspneumoniaPneumonia 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.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, BrazilWeb of ScienceConselho 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)FAPEMIG: RED-00140-16PRPQ-UFMG: 23853FAPESP:12/10653-9, 14/22909-3Frontiers Media Sa2020-07-08T13:09:40Z2020-07-08T13:09:40Z2018info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion-application/pdfhttp://dx.doi.org/10.3389/fimmu.2018.00142Frontiers In Immunology. Lausanne, v. 9, p. -, 2018.10.3389/fimmu.2018.00142WOS000425521100001.pdf1664-3224https://repositorio.unifesp.br/handle/11600/54123WOS:000425521100001engFrontiers In ImmunologyLausanneinfo:eu-repo/semantics/openAccessGalvao, 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.reponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESP2024-08-11T05:32:45Zoai:repositorio.unifesp.br/:11600/54123Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestbiblioteca.csp@unifesp.bropendoar:34652024-08-11T05:32:45Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
dc.title.none.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.por.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.none.fl_str_mv |
2018 2020-07-08T13:09:40Z 2020-07-08T13:09:40Z |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.3389/fimmu.2018.00142 Frontiers In Immunology. Lausanne, v. 9, p. -, 2018. 10.3389/fimmu.2018.00142 WOS000425521100001.pdf 1664-3224 https://repositorio.unifesp.br/handle/11600/54123 WOS:000425521100001 |
url |
http://dx.doi.org/10.3389/fimmu.2018.00142 https://repositorio.unifesp.br/handle/11600/54123 |
identifier_str_mv |
Frontiers In Immunology. Lausanne, v. 9, p. -, 2018. 10.3389/fimmu.2018.00142 WOS000425521100001.pdf 1664-3224 WOS:000425521100001 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Frontiers In Immunology |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
- application/pdf |
dc.coverage.none.fl_str_mv |
Lausanne |
dc.publisher.none.fl_str_mv |
Frontiers Media Sa |
publisher.none.fl_str_mv |
Frontiers Media Sa |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da UNIFESP instname:Universidade Federal de São Paulo (UNIFESP) instacron:UNIFESP |
instname_str |
Universidade Federal de São Paulo (UNIFESP) |
instacron_str |
UNIFESP |
institution |
UNIFESP |
reponame_str |
Repositório Institucional da UNIFESP |
collection |
Repositório Institucional da UNIFESP |
repository.name.fl_str_mv |
Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP) |
repository.mail.fl_str_mv |
biblioteca.csp@unifesp.br |
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1814268354272165888 |