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FXR/TGR5 mediates inflammasome activation and host resistance to bacterial infection

Bacterial infections are a major cause of chronic infections and mortality. Innate immune control is crucial for protection against bacterial pathogens. Bile acids facilitate intestinal absorption of lipid-soluble nutrients and modulate various metabolic pathways through the farnesoid X receptor (FX...

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Autores principales: Kang, Ju-Hee, Kim, Minji, Yim, Mijung
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8214033/
https://www.ncbi.nlm.nih.gov/pubmed/34179517
http://dx.doi.org/10.1016/j.bbrep.2021.101051
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author Kang, Ju-Hee
Kim, Minji
Yim, Mijung
author_facet Kang, Ju-Hee
Kim, Minji
Yim, Mijung
author_sort Kang, Ju-Hee
collection PubMed
description Bacterial infections are a major cause of chronic infections and mortality. Innate immune control is crucial for protection against bacterial pathogens. Bile acids facilitate intestinal absorption of lipid-soluble nutrients and modulate various metabolic pathways through the farnesoid X receptor (FXR) and Takeda G-protein-coupled receptor 5 (TGR5). Here, we identified a new role of FXR and TGR5 in promoting inflammasome activation during bacterial infection. Caspase-1/11 activation and release of cleaved interleukin (IL)-1β in FXR- and TGR5-deficient mouse bone marrow-derived macrophages upon Listeria monocytogenes or Escherichia coli infection was significantly reduced. In contrast, FXR- or TGR5-deficiency did not affect the transcription of caspase-1/11 and IL-1β. Inflammasome activation is critical for host immune defense against bacterial infections. Consistent with this, the deletion of FXR or TGR5 impaired effective clearance of L. monocytogenes or E. coli in vitro and in vivo, which was associated with greater mortality and bacterial burden than that of wild-type mice. Pretreatment with an FXR agonist decreased bacterial burden in vitro and increased survival in vivo. Thus, FXR and TGR5 promote inflammasome-mediated antimicrobial responses and may represent novel antibacterial therapeutic targets.
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spelling pubmed-82140332021-06-25 FXR/TGR5 mediates inflammasome activation and host resistance to bacterial infection Kang, Ju-Hee Kim, Minji Yim, Mijung Biochem Biophys Rep Research Article Bacterial infections are a major cause of chronic infections and mortality. Innate immune control is crucial for protection against bacterial pathogens. Bile acids facilitate intestinal absorption of lipid-soluble nutrients and modulate various metabolic pathways through the farnesoid X receptor (FXR) and Takeda G-protein-coupled receptor 5 (TGR5). Here, we identified a new role of FXR and TGR5 in promoting inflammasome activation during bacterial infection. Caspase-1/11 activation and release of cleaved interleukin (IL)-1β in FXR- and TGR5-deficient mouse bone marrow-derived macrophages upon Listeria monocytogenes or Escherichia coli infection was significantly reduced. In contrast, FXR- or TGR5-deficiency did not affect the transcription of caspase-1/11 and IL-1β. Inflammasome activation is critical for host immune defense against bacterial infections. Consistent with this, the deletion of FXR or TGR5 impaired effective clearance of L. monocytogenes or E. coli in vitro and in vivo, which was associated with greater mortality and bacterial burden than that of wild-type mice. Pretreatment with an FXR agonist decreased bacterial burden in vitro and increased survival in vivo. Thus, FXR and TGR5 promote inflammasome-mediated antimicrobial responses and may represent novel antibacterial therapeutic targets. Elsevier 2021-06-13 /pmc/articles/PMC8214033/ /pubmed/34179517 http://dx.doi.org/10.1016/j.bbrep.2021.101051 Text en © 2021 The Authors. Published by Elsevier B.V. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research Article
Kang, Ju-Hee
Kim, Minji
Yim, Mijung
FXR/TGR5 mediates inflammasome activation and host resistance to bacterial infection
title FXR/TGR5 mediates inflammasome activation and host resistance to bacterial infection
title_full FXR/TGR5 mediates inflammasome activation and host resistance to bacterial infection
title_fullStr FXR/TGR5 mediates inflammasome activation and host resistance to bacterial infection
title_full_unstemmed FXR/TGR5 mediates inflammasome activation and host resistance to bacterial infection
title_short FXR/TGR5 mediates inflammasome activation and host resistance to bacterial infection
title_sort fxr/tgr5 mediates inflammasome activation and host resistance to bacterial infection
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8214033/
https://www.ncbi.nlm.nih.gov/pubmed/34179517
http://dx.doi.org/10.1016/j.bbrep.2021.101051
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