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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Galvao, Izabela [1] ; Tavares, Luciana P. [1] ; Correa, Renan O. [2] ; Fachi, Jose Luis [2] ; Rocha, Vitor Melo [1] ; Rungue, Marcela [1] ; Garcia, Cristiana C. [3] ; Cassali, Geovanni [4] ; Ferreira, Caroline M. [5] ; Martins, Flaviano S. [6] ; Oliveira, Sergio C. [1] ; Mackay, Charles R. [7] ; Teixeira, Mauro M. [1] ; Vinolo, Marco Aurelio R. [2] ; Vieira, Angelica T. [1]
Total Authors: 15
[1] Univ Fed Minas Gerais, Inst Biol Sci, Dept Biochem & Immunol, Belo Horizonte, MG - Brazil
[2] Univ Estadual Campinas, Inst Biol, Dept Genet Evolut & Bioagents, Campinas, SP - Brazil
[3] Fiocruz MS, Inst Oswaldo Cruz, Lab Resp Viruses & Measles, Rio De Janeiro - Brazil
[4] Univ Fed Minas Gerais, Inst Biol Sci, Dept Gen Pathol, Belo Horizonte, MG - Brazil
[5] Univ Fed Sao Paulo, Inst Environm Chem & Pharmaceut Sci, Dept Pharmaceut Sci, Diadema - Brazil
[6] Univ Fed Minas Gerais, Inst Biol Sci, Dept Microbiol, Belo Horizonte, MG - Brazil
[7] Monash Univ, Dept Immunol, Melborne, Vic - Australia
Total Affiliations: 7
Document type: Journal article
Source: FRONTIERS IN IMMUNOLOGY; v. 9, FEB 20 2018.
Web of Science Citations: 7

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. (AU)

FAPESP's process: 14/22909-3 - Role of the short chain fatty acids and their receptor (GPR43) in the neutrophil death induced by anaerobic bacteria
Grantee:Erica Moraes Sernaglia
Support type: Scholarships in Brazil - Master
FAPESP's process: 12/10653-9 - Role of short chain fatty acids and their receptor (GPR43) in the immune response to anaerobic bacteria in vivo and in vitro
Grantee:Marco Aurélio Ramirez Vinolo
Support type: Research Grants - Young Investigators Grants