The Metabolic Sensor GPR43 Receptor Plays a Role in the Control of Klebsiella Pneumoniae Infection in the Lung

Detalhes bibliográficos
Autor(a) principal: Galvao, Izabela
Data de Publicação: 2018
Outros Autores: 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.
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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spelling 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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