The metabolic sensor GPR43 receptor plays a role in the control of Klebsiella pneumoniae infection in the lung

Izabela Galvão, Luciana P. Tavares, Renan O. Corrêa, José Luís Fachi, Vitor Melo Rocha, Marcela Rungue, Cristiana C. Garcia, Geovanni Cassali, Caroline M. Ferreira, Flaviano S. Martins, Sergio C. Oliveira, Charles R. Mackay, Mauro M. Teixeira, Marco Aurélio R. Vinolo, Angélica T. Vieira

Research output: Contribution to journalArticleResearchpeer-review

7 Citations (Scopus)

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.

Original languageEnglish
Article number142
Number of pages11
JournalFrontiers in Immunology
Volume9
DOIs
Publication statusPublished - 20 Feb 2018

Keywords

  • GPR43
  • Inflammation
  • Lung infection
  • Microbiota
  • Pneumonia
  • Short-chain fatty acids

Cite this

Galvão, I., Tavares, L. P., Corrêa, R. O., Fachi, J. L., Rocha, V. M., Rungue, M., ... Vieira, A. T. (2018). The metabolic sensor GPR43 receptor plays a role in the control of Klebsiella pneumoniae infection in the lung. Frontiers in Immunology, 9, [142]. https://doi.org/10.3389/fimmu.2018.00142
Galvão, Izabela ; Tavares, Luciana P. ; Corrêa, Renan O. ; Fachi, José Luís ; Rocha, Vitor Melo ; Rungue, Marcela ; Garcia, Cristiana C. ; Cassali, Geovanni ; Ferreira, Caroline M. ; Martins, Flaviano S. ; Oliveira, Sergio C. ; Mackay, Charles R. ; Teixeira, Mauro M. ; Vinolo, Marco Aurélio R. ; Vieira, Angélica T. / The metabolic sensor GPR43 receptor plays a role in the control of Klebsiella pneumoniae infection in the lung. In: Frontiers in Immunology. 2018 ; Vol. 9.
@article{420ce1d5dd5a481dbaa583fa445e8255,
title = "The metabolic sensor GPR43 receptor plays a role in the control of Klebsiella pneumoniae infection in the lung",
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 = "GPR43, Inflammation, Lung infection, Microbiota, Pneumonia, Short-chain fatty acids",
author = "Izabela Galv{\~a}o and Tavares, {Luciana P.} and Corr{\^e}a, {Renan O.} and Fachi, {Jos{\'e} Lu{\'i}s} and Rocha, {Vitor Melo} and Marcela Rungue and Garcia, {Cristiana C.} and Geovanni Cassali and Ferreira, {Caroline M.} and Martins, {Flaviano S.} and Oliveira, {Sergio C.} and Mackay, {Charles R.} and Teixeira, {Mauro M.} and Vinolo, {Marco Aur{\'e}lio R.} and Vieira, {Ang{\'e}lica T.}",
year = "2018",
month = "2",
day = "20",
doi = "10.3389/fimmu.2018.00142",
language = "English",
volume = "9",
journal = "Frontiers in Immunology",
issn = "1664-3224",
publisher = "Frontiers Media",

}

Galvão, I, Tavares, LP, Corrêa, RO, Fachi, JL, Rocha, VM, Rungue, M, Garcia, CC, Cassali, G, Ferreira, CM, Martins, FS, Oliveira, SC, Mackay, CR, Teixeira, MM, Vinolo, MAR & Vieira, AT 2018, 'The metabolic sensor GPR43 receptor plays a role in the control of Klebsiella pneumoniae infection in the lung', Frontiers in Immunology, vol. 9, 142. https://doi.org/10.3389/fimmu.2018.00142

The metabolic sensor GPR43 receptor plays a role in the control of Klebsiella pneumoniae infection in the lung. / Galvão, Izabela; Tavares, Luciana P.; Corrêa, Renan O.; Fachi, José Luís; Rocha, Vitor Melo; Rungue, Marcela; Garcia, Cristiana C.; Cassali, Geovanni; Ferreira, Caroline M.; Martins, Flaviano S.; Oliveira, Sergio C.; Mackay, Charles R.; Teixeira, Mauro M.; Vinolo, Marco Aurélio R.; Vieira, Angélica T.

In: Frontiers in Immunology, Vol. 9, 142, 20.02.2018.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - The metabolic sensor GPR43 receptor plays a role in the control of Klebsiella pneumoniae infection in the lung

AU - Galvão, Izabela

AU - Tavares, Luciana P.

AU - Corrêa, Renan O.

AU - Fachi, José Luís

AU - Rocha, Vitor Melo

AU - Rungue, Marcela

AU - Garcia, Cristiana C.

AU - Cassali, Geovanni

AU - Ferreira, Caroline M.

AU - Martins, Flaviano S.

AU - Oliveira, Sergio C.

AU - Mackay, Charles R.

AU - Teixeira, Mauro M.

AU - Vinolo, Marco Aurélio R.

AU - Vieira, Angélica T.

PY - 2018/2/20

Y1 - 2018/2/20

N2 - 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.

AB - 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.

KW - GPR43

KW - Inflammation

KW - Lung infection

KW - Microbiota

KW - Pneumonia

KW - Short-chain fatty acids

UR - http://www.scopus.com/inward/record.url?scp=85042323528&partnerID=8YFLogxK

U2 - 10.3389/fimmu.2018.00142

DO - 10.3389/fimmu.2018.00142

M3 - Article

VL - 9

JO - Frontiers in Immunology

JF - Frontiers in Immunology

SN - 1664-3224

M1 - 142

ER -