Proteomics

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The cytosolic DNA sensor cGAS recognizes Neutrophil Extracellular Traps


ABSTRACT: Neutrophil Extracellular Traps (NETs) are structures consisting of chromatin and antimicrobial molecules that are released by neutrophils during a form of regulated cell death called NETosis. NETs trap invading pathogens, promote coagulation and activate myeloid cells to produce Type I interferons (type I IFN), proinflammatory cytokines that regulate the immune system. The mechanism of NET recognition by myeloid cells is not yet clearly identified. Here we show that macrophages and other myeloid cells phagocytose NETs. Once in phagosomes, NETs translocate to the cytosol, where they activate the DNA sensor cyclic GMP-AMP synthase (cGAS) and induce type I IFN expression. cGAS recognizes the DNA backbone of NETs. Interestingly, the NET associated serine protease Neutrophil Elastase (NE) mediates the activation of the pathway. We confirmed that NETs activate cGAS in vivo. Thus, our findings identify cGAS as a major sensor of NETs, mediating the immune activation during infection and in auto-immune diseases.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Christian Frese  

LAB HEAD: Christian K. Frese

PROVIDER: PXD015579 | Pride | 2021-02-18

REPOSITORIES: Pride

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L1_190919_19M027_set1_1.raw Raw
L1_190919_19M027_set1_2.raw Raw
L1_190919_19M027_set1_3.raw Raw
L1_190919_19M027_set1_4.raw Raw
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