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

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

Author Galvao, Izabela Google Scholar
Tavares, Luciana P. Google Scholar
Correa, Renan O. Google Scholar
Fachi, Jose Luis Google Scholar
Rocha, Vitor Melo Google Scholar
Rungue, Marcela Google Scholar
Garcia, Cristiana C. Google Scholar
Cassali, Geovanni Google Scholar
Ferreira, Caroline M. Autor UNIFESP Google Scholar
Martins, Flaviano S. Google Scholar
Oliveira, Sergio C. Google Scholar
Mackay, Charles R. Google Scholar
Teixeira, Mauro M. Google Scholar
Vinolo, Marco Aurelio R. Google Scholar
Vieira, Angelica T. Google Scholar
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.
Keywords lung infection
GPR43
inflammation
microbiota
short-chain fatty acids
pneumonia
xmlui.dri2xhtml.METS-1.0.item-coverage Lausanne
Language English
Sponsor 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)
Grant number FAPEMIG: RED-00140-16
PRPQ-UFMG: 23853
FAPESP:12/10653-9, 14/22909-3
Date 2018
Published in Frontiers In Immunology. Lausanne, v. 9, p. -, 2018.
ISSN 1664-3224 (Sherpa/Romeo, impact factor)
Publisher Frontiers Media Sa
Extent -
Origin http://dx.doi.org/10.3389/fimmu.2018.00142
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000425521100001
URI https://repositorio.unifesp.br/handle/11600/54123

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