The Metabolic Sensor GPR43 Receptor Plays a Role in the Control of Klebsiella pneumoniae Infection in the Lung
Autor: | Luciana P. Tavares, Vitor T M Rocha, Charles R. Mackay, Cristiana C. Garcia, Flaviano S. Martins, Geovanni Dantas Cassali, Izabela Galvão, Caroline M. Ferreira, Angélica T. Vieira, Marco Aurélio Ramirez Vinolo, Mauro M. Teixeira, Marcela Rungue, Renan O. Corrêa, Sergio C. Oliveira, José Luís Fachi |
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Rok vydání: | 2018 |
Předmět: |
lcsh:Immunologic diseases. Allergy
0301 basic medicine Phagocytosis short-chain fatty acids 030106 microbiology Immunology Inflammation Biology Gut flora Microbiology 03 medical and health sciences Immune system microbiota medicine pneumonia Immunology and Allergy Pathogen Lung lung infection GPR43 biology.organism_classification medicine.disease 030104 developmental biology medicine.anatomical_structure inflammation Increased inflammatory response medicine.symptom lcsh:RC581-607 Pneumonia (non-human) |
Zdroj: | Frontiers in Immunology, Vol 9 (2018) |
ISSN: | 1664-3224 |
Popis: | 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. |
Databáze: | OpenAIRE |
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