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Reprogramming of pro-inflammatory human macrophages to an anti-inflammatory phenotype by bile acids

ABSTRACT: Reprogramming of pro-inflammatory human macrophages to an anti-inflammatory phenotype by bile acids

PROVIDER: PRJNA814644 | ENA |

REPOSITORIES: ENA

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Reprogramming of pro-inflammatory human macrophages to an anti-inflammatory phenotype by bile acids

Project description:Cholestasis is caused by autoimmune reactions, drug-induced hepatotoxicity, viral infections of the liver and the obstruction of bile ducts by tumours or gallstones. Cholestatic conditions are associated with impaired innate and adaptive immunity, including alterations of the cellular functions of monocytes, macrophages, NK cells and T-cells. Bile acids act as signalling molecules, affecting lipopolysaccharide (LPS)-induced cytokine expression in primary human macrophages. The present manuscript investigates the impact of bile acids, such as taurolithocholic acid (TLC), on the transcriptome of human macrophages in the presence or absence of LPS. While TLC itself has almost no effect on gene expression under control conditions, this compound modulates the expression of 202 out of 865 transcripts in the presence of LPS. Interestingly, pathway analysis revealed that TLC specifically supressed the expression of genes involved in mediating pro-inflammatory effects, phagocytosis, interactions with pathogens and autophagy as well as the recruitment of immune cells, such as NK cells, neutrophils and T cells. These data indicate a broad influence of bile acids on inflammatory responses and immune functions in macrophages. These findings may contribute to the clinical observation that patients with cholestasis present a lack of response to bacterial or viral infections.

2022-03-11 | GSE198326 | GEO

Reprogramming of pro-inflammatory human macrophages to an anti-inflammatory phenotype by bile acids.

Project description: Not available

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Effect of Bile Acids on C. difficile Growth

Project description:Clostridium difficile epidemic strain R20291 was grown in presence of the two main bile acids, Deoxycholate and Cholate.

2019-08-28 | GSE86152 | GEO

Deoxyhypusine Synthase Promotes a Pro-Inflammatory Macrophage Phenotype

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Differential view on the bile acids stress response of Clostridioides difficile

Project description:In this study, we aimed at the characterization of C. difficile’s stress response to the main four human bile acids. Although, a phenotypically description of growth differences upon challenge with different bile acids has been described (Lewis 2016, Thanissery 2017), there is no information on the adaptation of gene expression available. We employed a comprehensive proteomics approach to record stress signatures of the unconjugated bile acids CA, CDCA, DCA and LCA in shock experiments as well as during long-term-stress conditions and could depict a general stress response concerning all four bile acids, but also specific responses to only a single or a few of the different bile acids. Our results are a starting point for the understanding of how the individual bile acids cocktail of a patient can decide on the outcome of a C. difficile infection.

2019-02-12 | PXD010514 | Pride

Differential view on the bile acids stress response of Clostridioides difficile_longterm stress

Project description:In this study, we aimed at the characterization of C. difficile’s stress response to the main four human bile acids. Although, a phenotypically description of growth differences upon challenge with different bile acids has been described (Lewis 2016, Thanissery 2017), there is no information on the adaptation of gene expression available. We employed a comprehensive proteomics approach to record stress signatures of the unconjugated bile acids CA, CDCA, DCA and LCA during long-term-stress conditions and could depict a general stress response concerning all four bile acids, but also specific responses to only a single or a few of the different bile acids. Our results are a starting point for the understanding of how the individual bile acids cocktail of a patient can decide on the outcome of a C. difficile infection

2019-02-09 | PXD010525 | Pride

Eggerthella lenta DSM 2243 alleviates bile acid stress response in Clostridium ramosum and Anaerostipes cacae by transformation of bile acids

Project description:Bile acids are not only crucial for the uptake of lipids, but also have widespread systematic ef-fects and shape the gut-microbiome composition. Bile acids can directly shape the gut-microbiome and can be modified by bacteria such as Eggerthella lenta which in turn plays a crucial role in host metabolism and immune response. We cultivated eight strains that represent a simplified human intestinal microbiome and inves-tigated the molecular response to bile acids, co-culturing with Eggerthella lenta and the combina-tion. We observed growth inhibition of particularly gram-positive strains during bile acid stress, which could be alleviated through co-culturing with Eggerthella lenta. The inhibition of growth was related to a decrease in membrane integrity and genotoxic effects of bile acids, which we investigated using zeta potential measurements in combination with proteomic and metabolomic analyses. Co-culturing with Eggerthella lenta alleviated stress through formation of oxidized and epimer-ized bile acids and the molecular response to co-culturing was seen to be strain specific. We also note that we could detect the recently described Microbial Bile Salt Conjugates in our cultures. This study highlights the significance of a potent bile acid modifier and how in-depth molecular analyses are required to decipher cross-communication between gut and host.

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The effect of bile acids on human placental proteome

Project description:The effects of bile acids on human placental proteome was examined

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Secondary bile acids function through the vitamin D receptor in myeloid progenitor cells to promote myelopoiesis

Project description:Metabolic products of the microbiota can alter hematopoiesis. However, the contribution and site of action of bile acids is poorly understood. Here we demonstrate that the secondary bile acids, deoxycholic acid (DCA), and lithocholic acid (LCA) increase bone marrow myelopoiesis. Treatment of bone marrow cells with DCA and LCA preferentially expanded immunophenotypic and functional (CFU-GM) granulocyte-monocyte progenitors (GMPs). DCA treatment of sorted hematopoietic stem/progenitor cells (HSPCs) increased CFU-GMs, indicating that direct exposure of HSPCs to DCA sufficed to expand GMPs. We determined that the vitamin D receptor (VDR) was required for the DCA-induced increase in CFU-GMs and GMPs. Finally, single-cell RNA sequencing revealed that DCA significantly upregulated genes associated with myeloid differentiation and proliferation in GMPs. The action of DCA on HSPCs to expand GMPs in a VDR-dependent manner suggests a mechanism for how microbiome-host interactions may directly impact bone marrow hematopoiesis and the severity of infectious and inflammatory disease.

2023-07-01 | GSE215639 | GEO