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Myeloid ATG7 Functions as a Sentinel for Pulmonary Defense Against Infection with Nontuberculous Mycobacteria

ABSTRACT: Myeloid ATG7 Functions as a Sentinel for Pulmonary Defense Against Infection with Nontuberculous Mycobacteria

PROVIDER: PRJNA1110168 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR28988131_1.fastq.gz	Fastqsanger.gz
	SRR28988131_2.fastq.gz	Fastqsanger.gz
	SRR28988132_1.fastq.gz	Fastqsanger.gz
	SRR28988132_2.fastq.gz	Fastqsanger.gz
	SRR28988133_1.fastq.gz	Fastqsanger.gz

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Myeloid ATG7 Functions as a Sentinel for Pulmonary Defense Against Infection with Nontuberculous Mycobacteria

Project description:Nontuberculous mycobacterial pulmonary diseases (NTM-PD) are becoming increasingly prevalent and incident, and heightened antibiotic resistance presents a considerable challenge to clinicians. Despite this, our understanding of the factor(s) contributing to host defense against NTM-PD remains incomplete. Herein, we report that the myeloid autophagy-related gene (ATG) 7 promotes host protective responses against NTM-PD by mitigating excessive pathological inflammation, oxidative stress, and cell death associated with neutrophil infiltration. Patients with NTM-PD displayed a notable reduction in ATG7 expression in peripheral blood mononuclear cells and in necrotic lesions at disease sites. Mice with deletion of Atg7 specifically in myeloid cells (Atg7 cKO) exhibited a significant increase in lung bacterial load during infection. Spatial and bulk RNA-seq analyses, as well as biological experiments, revealed heightened myeloid cell infiltration, excessive inflammation, and mitochondrial damage in Atg7 cKO lung tissues. Furthermore, ｍyeloid Atg7-deficient mice showed upregulated apoptosis, necrosis, and GSDME-associated cell death, along with the formation of neutrophil extracellular traps, in the lung tissues during NTM-PD. However, Atg7-deficient macrophages showed only marginal differences in inflammation and cell death in vitro during NTM infection. Our findings demonstrate that myeloid ATG7 plays a major role in non-cell-autonomous protection against NTM-PD by alleviating neutrophil-associated pathological inflammation and cell death.

2025-05-20 | GSE267176 | GEO

Spatial transcriptomics of Atg7 knockout mice reveals ATG7’s role in antimicrobial immunity against nontuberculous mycobacteria

Project description:We performed Spatial transcriptomics (Visium) using the 10X Genomics platform to investigate the role of the autophagy-related protein ATG7 in the context of nontuberculous mycobacterial (NTM) infection. ATG7 in innate immune cells plays a critical role in controlling NTM infection and protecting lung tissue from pathological inflammation. This study represents single-cell analysis of Mice deletion of Atg7 in innate immune cells and reveals the importance of ATG7 in mediating antimicrobial responses during infection and its essential role in host defense mechanisms against NTM.

2025-07-09 | GSE297621 | GEO

Single-cell RNA-seq of Atg7 knockout mice reveals ATG7’s role in antimicrobial immunity against nontuberculous mycobacteria

Project description:We performed single-cell RNA sequencing (scRNA-seq) using the 10X Genomics platform to investigate the role of the autophagy-related protein ATG7 in the context of nontuberculous mycobacterial (NTM) infection. ATG7 in innate immune cells plays a critical role in controlling NTM infection and protecting lung tissue from pathological inflammation. This study represents single-cell analysis of Mice deletion of Atg7 in innate immune cells and reveals the importance of ATG7 in mediating antimicrobial responses during infection and its essential role in host defense mechanisms against NTM.

2025-07-09 | GSE297620 | GEO

Nontuberculous mycobacteria

Project description:Nontuberculous mycobacteria Metagenome

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Spatial transcriptomics of Atg7 knockout mice reveals ATG7’s role in antimicrobial immunity against nontuberculous mycobacteria

Project description:Spatial transcriptomics of Atg7 knockout mice reveals ATG7’s role in antimicrobial immunity against nontuberculous mycobacteria

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Single-cell RNA-seq of Atg7 knockout mice reveals ATG7’s role in antimicrobial immunity against nontuberculous mycobacteria

Project description:Single-cell RNA-seq of Atg7 knockout mice reveals ATG7’s role in antimicrobial immunity against nontuberculous mycobacteria

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Nontuberculous mycobacteria (NTM)

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Gene signature profiles in respiratory epithelium infected with nontuberculous mycobacteria

Project description:The incidence of pulmonary nontuberculous mycobacterial (PNTM) disease is increasing, but host susceptibility factors are not fully understood. We infected air-liquid interface (ALI) primary respiratory epithelial cell cultures with Mycobacterium avium complex (MAC) or Mycobacterium abscessus (MAB) and performed transcriptome sequencing (RNA-Seq) to identify relevant gene expression differences. We used cells from 4 different donors in order to try to obtain generalizable data. The differentiated respiratory epithelial cells in ALI were infected with MAC or MAB at MOI of 100:1 or 1000:1, and RNA-seq was performed at 1 and 3 days after infection. We found downregulation of ciliary genes, including several identified with polymorphisms in previous PNTM cohorts. The cytokine IL-32, the superpathway of cholesterol biosynthesis and downstream targets within the IL-17 signaling pathway were all elevated. The integrin signaling pathway was more upregulated by MAB than MAC infection. Working with primary respiratory epithelial cells infected with nontuberculous mycobacteria at ALI, we identified ciliary function, cholesterol biosynthesis, chemokine production and the IL-17 pathway as major targets of host responses to infection. Some of these pathways may be amenable to therapeutic manipulation.

2017-10-13 | GSE93526 | GEO

mycobacteria

Project description:Temperature and pH growth preferences of nontuberculous mycobacteria - Genomic sequencing, Raw sequence reads

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