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BROAD TRANSCRIPTIONAL FIRING REPRESSES BACTERICIDAL ACTIVITY IN HUMAN AIRWAY NEUTROPHILS

ABSTRACT: BROAD TRANSCRIPTIONAL FIRING REPRESSES BACTERICIDAL ACTIVITY IN HUMAN AIRWAY NEUTROPHILS

PROVIDER: PRJNA693842 | ENA |

REPOSITORIES: ENA

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Broad transcriptional firing represses bactericidal activity in human airway neutrophils

Project description:Broad transcriptional firing represses bactericidal activity in human airway neutrophils

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Broad transcriptional firing represses bactericidal activity in human airway neutrophils [Transcriptional_Blockage_CFASN_Neutrophils]

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Broad transcriptional firing represses bactericidal activity in human airway neutrophils [10hours_transmigrated_CFASN_Neutrophils]

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BROAD TRANSCRIPTIONAL FIRING REPRESSES BACTERICIDAL ACTIVITY IN HUMAN AIRWAY NEUTROPHILS

Project description:Neutrophils are often considered terminally differentiated and poised for bacterial killing. In chronic diseases such as cystic fibrosis (CF), an unexplained paradox pits massive neutrophil presence against prolonged bacteria infections. Here, we show that neutrophils recruited to CF airways in vivo and in an in vitro transmigration model display rapid and broad transcriptional firing, leading to an upregulation of survival and anabolic genes, and a downregulation of antimicrobial genes. Newly transcribed RNAs are mirrored by the appearance of corresponding proteins, confirming active translation in these cells. Remarkably, treatment by the RNA polymerase II and III inhibitor alpha-amanitin restored expression of key antimicrobial genes, and increased bactericidal capacity of CF airway neutrophils in vitro and in short-term sputum cultures ex vivo. Broadly, our findings show that neutrophil plasticity is regulated at the terminal organ via RNA and protein synthesis, leading to adaptations that profoundly impact their canonical functions (i.e., bacterial clearance).

2021-01-22 | GSE165265 | GEO

Broad transcriptional firing represses bactericidal activity in human airway neutrophils [Transcriptional_Blockage_CFASN_Neutrophils]

Project description:Neutrophils are often considered terminally differentiated and poised for bacterial killing. In chronic diseases such as cystic fibrosis (CF), an unexplained paradox pits massive neutrophil presence against prolonged bacteria infections. Here, we show that neutrophils recruited to CF airways in vivo and in an in vitro transmigration model display rapid and broad transcriptional firing, leading to an upregulation of survival and anabolic genes, and a downregulation of antimicrobial genes. Newly transcribed RNAs are mirrored by the appearance of corresponding proteins, confirming active translation in these cells. Remarkably, treatment by the RNA polymerase II and III inhibitor Alpha-amanitin restored expression of key antimicrobial genes, and increased bactericidal capacity of CF airway neutrophils in vitro and in short-term sputum cultures ex vivo. Broadly, our findings show that neutrophil plasticity is regulated at the terminal organ via RNA and protein synthesis, leading to adaptations that profoundly impact their canonical functions (i.e., bacterial clearance).

2021-02-19 | GSE167066 | GEO

Broad transcriptional firing represses bactericidal activity in human airway neutrophils [10hours_transmigrated_CFASN_Neutrophils]

Project description:In this model, naïve blood neutrophils are migrated through a small airway epithelium grown at air-liquid interface toward CF airway fluid supernatant (CFASN, which corresponds to sputum sequentially centrifuged to remove cells and bacteria) or leukotriene B4 (LTB4, transmigration control), placed apically.

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Broad transcriptional firing represses bactericidal activity in human airway neutrophils

Project description:This SuperSeries is composed of the SubSeries listed below.

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Transcriptional firing represses bactericidal activity in cystic fibrosis airway neutrophils.

Project description: Not available

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Prenylcysteine oxidase 1 like protein is required for neutrophil bactericidal activities

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2023-05-01 | GSE217064 | GEO

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