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

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dc.contributor.author Galvao, Izabela
dc.contributor.author Tavares, Luciana P.
dc.contributor.author Correa, Renan O.
dc.contributor.author Fachi, Jose Luis
dc.contributor.author Rocha, Vitor Melo
dc.contributor.author Rungue, Marcela
dc.contributor.author Garcia, Cristiana C.
dc.contributor.author Cassali, Geovanni
dc.contributor.author Ferreira, Caroline M. [UNIFESP]
dc.contributor.author Martins, Flaviano S.
dc.contributor.author Oliveira, Sergio C.
dc.contributor.author Mackay, Charles R.
dc.contributor.author Teixeira, Mauro M.
dc.contributor.author Vinolo, Marco Aurelio R.
dc.contributor.author Vieira, Angelica T.
dc.date.accessioned 2020-07-08T13:09:40Z
dc.date.available 2020-07-08T13:09:40Z
dc.date.issued 2018
dc.identifier http://dx.doi.org/10.3389/fimmu.2018.00142
dc.identifier.citation Frontiers In Immunology. Lausanne, v. 9, p. -, 2018.
dc.identifier.issn 1664-3224
dc.identifier.uri https://repositorio.unifesp.br/handle/11600/54123
dc.description.abstract 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. en
dc.description.sponsorship Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)
dc.description.sponsorship Coordenacnao de aperfeicoamento de pessoal de Nivel Superior (CAPES)
dc.description.sponsorship Rede Mineira de Imunobiologicos from the Fundacao de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG)
dc.description.sponsorship Australian National Health and Medical Research Council (NHMRC)
dc.description.sponsorship Pro-reitoria de Pesquisa, Universidade Federal de Minas Gerais (PRPQ-UFMG)
dc.description.sponsorship Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)
dc.description.sponsorship Fundacao de Desenvolvimento da Unicamp (Funcamp)
dc.format.extent -
dc.language.iso eng
dc.publisher Frontiers Media Sa
dc.relation.ispartof Frontiers In Immunology
dc.rights Acesso aberto
dc.subject lung infection en
dc.subject GPR43 en
dc.subject inflammation en
dc.subject microbiota en
dc.subject short-chain fatty acids en
dc.subject pneumonia en
dc.title The Metabolic Sensor GPR43 Receptor Plays a Role in the Control of Klebsiella Pneumoniae Infection in the Lung en
dc.type Artigo
dc.description.affiliation Univ Fed Minas Gerais, Inst Biol Sci, Dept Biochem & Immunol, Belo Horizonte, MG, Brazil
dc.description.affiliation Univ Estadual Campinas, Inst Biol, Dept Genet Evolut & Bioagents, Campinas, SP, Brazil
dc.description.affiliation Fiocruz MS, Inst Oswaldo Cruz, Lab Resp Viruses & Measles, Rio De Janeiro, Brazil
dc.description.affiliation Univ Fed Minas Gerais, Inst Biol Sci, Dept Gen Pathol, Belo Horizonte, MG, Brazil
dc.description.affiliation Univ Fed Sao Paulo, Inst Environm Chem & Pharmaceut Sci, Dept Pharmaceut Sci, Diadema, Brazil
dc.description.affiliation Univ Fed Minas Gerais, Inst Biol Sci, Dept Microbiol, Belo Horizonte, MG, Brazil
dc.description.affiliation Monash Univ, Dept Immunol, Melborne, Vic, Australia
dc.description.affiliationUnifesp Univ Fed Sao Paulo, Inst Environm Chem & Pharmaceut Sci, Dept Pharmaceut Sci, Diadema, Brazil
dc.description.sponsorshipID FAPEMIG: RED-00140-16
dc.description.sponsorshipID PRPQ-UFMG: 23853
dc.description.sponsorshipID FAPESP:12/10653-9, 14/22909-3
dc.identifier.file WOS000425521100001.pdf
dc.identifier.doi 10.3389/fimmu.2018.00142
dc.description.source Web of Science
dc.identifier.wos WOS:000425521100001
dc.coverage Lausanne
dc.citation.volume 9



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