METTL3 Deficiency in Macrophage Aggravates Neutrophilic Asthma by Regulating ZBP1-NLRP3 Inflammasome Activation
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ABSTRACT:
PROVIDER: PRJNA1196358 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR31665376_1.fastq.gz | Fastqsanger.gz | |||
| SRR31665376_2.fastq.gz | Fastqsanger.gz | |||
| SRR31665377_1.fastq.gz | Fastqsanger.gz | |||
| SRR31665377_2.fastq.gz | Fastqsanger.gz | |||
| SRR31665378_1.fastq.gz | Fastqsanger.gz |
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Project description:The innate immune system recognizes nucleic acids as a signature of microbial infection and initiates host-protective responses, including the production of type I IFN and proinflammatory cytokines. Z-DNA binding protein 1 (ZBP1, also known as DLM-1 or DAI) was previously identified as a dsDNA binding protein, triggering DNA-mediated activation of innate immune responses. However, mice or cells lacking ZBP1 produce normal levels of type I IFN in response to dsDNA. Therefore, the classification of ZBP1 as a true DNA sensor remains to be resolved. Here, we report that the single stranded RNA virus, influenza A virus (IAV) is a trigger of the cytosolic sensor ZBP1. Sensing of IAV infection by ZBP1 engages a novel NLRP3 inflammasome pathway that is not defined by the conventions of the canonical and non-canonical NLRP3 inflammasome pathways. Surprisingly, IAV-induced cell death was not prevented by the absence of the NLRP3 inflammasome. Instead, we identified parallel contributions from pyroptosis, necroptosis and apoptosis in the execution of ZBP1-dependent cell death, mediated by the kinase RIPK3. Overall, the ability of ZBP1 to sense IAV infection signifies a point of divergence for IAV-induced programmed cell death pathways and inflammasome activation.
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