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

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

PROVIDER: PRJNA702819 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13741339_1.fastq.gz	Fastqsanger.gz
	SRR13741339_2.fastq.gz	Fastqsanger.gz
	SRR13741340_1.fastq.gz	Fastqsanger.gz
	SRR13741340_2.fastq.gz	Fastqsanger.gz
	SRR13741341_1.fastq.gz	Fastqsanger.gz

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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

| PRJNA702818 | ENA

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]

Project description: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

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.

2021-02-19 | GSE167069 | GEO

Broad transcriptional firing represses bactericidal activity in human airway neutrophils

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

2021-02-19 | GSE167070 | GEO

Transcriptional firing represses bactericidal activity in cystic fibrosis 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 bacterial 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 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. Treatment by the RNA polymerase II and III inhibitor α-amanitin restores the expression of key antimicrobial genes and increases the 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 site of inflammation via RNA and protein synthesis, leading to adaptations that affect their canonical functions (i.e., bacterial clearance).

| S-EPMC8080108 | biostudies-literature

Transcriptomic analysis of Per2-deficient neutrophils compared WT neutrophils following infection.

Project description:Functional analysis demonstrates that neutrophils deficient in Per2 have reduced bactericidal activity when compared WT neutrophils.

2024-09-27 | GSE244308 | GEO

Prenylcysteine oxidase 1 like protein is required for neutrophil bactericidal activities

Project description:The bactericidal function of neutrophils are dependent on myriad intrinsic and extrinsic stimuli. Using systems immunology approaches we identified microbiome- and infection-induced changes in neutrophils. We focused on investigating the Prenylcysteine oxidase 1 like (Pcyox1l) protein function. Murine and human Pcyox1l proteins share ninety four percent aminoacid homology revealing significant evolutionary conservation and implicating Pcyox1l in mediating important biological functions. Here we show that the loss of Pcyox1l protein results in significant reductions in the mevalonate pathway impacting autophagy and cellular viability under homeostatic conditions. Concurrently, Pcyox1l CRISPRed-out neutrophils exhibit deficient bactericidal properties. Pcyox1l knock-out mice demonstrate significant susceptibility to infection with the gram-negative pathogen P. aeruginosa exemplified through increased neutrophil infiltrates, hemorrhaging, and reduced bactericidal functionality. Cumulatively, we ascribe a function to Pcyox1l protein as a fundamental regulator of the prenylation pathway and suggest connections beween metabolic responses and neutrophil functionality. Anastasia Petenkova , Shelby A. Auger, Jeffrey Lamb, Daisy Quellier, Cody Carter, On TakTo, Jelena Milosevic, Rana Barghout, Abirami Kugadas, Xiaoxiao Lu, Jennifer Geddes-McAlister, Raina Fichorova, David B. Sykes, Mark D. Distefano, and Mihaela Gadjeva. 2023. Prenylcysteine oxidase 1 like protein is required for neutrophil bactericidal activities. Nat.Comm.

2023-04-14 | PXD031115 | Pride

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