Original Research ARTICLE
The metabolic sensor GPR43 receptor plays a role in the control of Klebsiella pneumonie infection in the lung
- 1Universidade Federal de Minas Gerais, Brazil
- 2Universidade Estadual de Campinas, Brazil
- 3Department of Biochemistry and Immunology, Universidade Federal de Minas Gerais, Brazil
- 4Fundação Oswaldo Cruz (Fiocruz), Brazil
- 5Department of Pathology, Universidade Federal de Minas Gerais, Brazil
- 6Federal University of São Paulo, Brazil
- 7Departamento de Microbiologia, Instituto de Ciências Biológicas - Universidade Federal de Minas Gerais UFMG, Brazil
- 8Biochemistry and Immunology, Universidade Federal de Minas Gerais, Brazil
- 9Monash Institute of Medical Research, Australia
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: microbiota and immunity, lung inflammation, mucosal immunity, GPR43, Short Chain Fatty Acids, Gut Microbiota, Infection Control, Pneumonia, Bacterial
Received: 26 Sep 2017;
Accepted: 16 Jan 2018.
Edited by:Ed C. Lavelle, Trinity College, Dublin, Ireland
Reviewed by:Harry D. Dawson, Agricultural Research Service (USDA), United States
Rosalinda Sorrentino, Università degli Studi di Salerno, Italy
Copyright: © 2018 Galvão, Tavares, Côrrea, Fachi, Rocha, Rungue, Garcia, Cassali, Ferreira, Martins, Oliveira, Mackay, Teixeira, Vinolo and Vieira. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Prof. Angelica T. Vieira, Universidade Federal de Minas Gerais, Department of Biochemistry and Immunology, Belo Horizonte, Brazil, firstname.lastname@example.org