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  The cytosolic DNA sensor cGAS recognizes neutrophil extracellular traps.

Apel, F., Andreeva, L., Knackstedt, L. S., Streeck, R., Frese, C. K., Goosmann, C., et al. (2021). The cytosolic DNA sensor cGAS recognizes neutrophil extracellular traps. Science Signaling, 14(673), eaax7942. doi:10.1126/scisignal.aax7942.

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Item Permalink: https://hdl.handle.net/21.11116/0000-0009-126D-9 Version Permalink: https://hdl.handle.net/21.11116/0000-000B-3C27-7
Genre: Journal Article

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 Creators:
Apel, Falko1, Author
Andreeva, Liudmila, Author
Knackstedt, Lorenz Sebastian1, Author
Streeck, Robert1, Author
Frese, Christian Karl2, Author
Goosmann, Christian1, Author
Hopfner, Karl-Peter, Author
Zychlinsky, Arturo1, Author
Affiliations:
1Max Planck Institute for Infection Biology, Max Planck Society, Charitéplatz 1, D-10117 Berlin, DE, ou_1664137              
2Max Planck Unit for the Science of Pathogens, Max Planck Society, ou_3213696              

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 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 (IFNs), proinflammatory cytokines that regulate the immune system. Here, we showed that macrophages and other myeloid cells phagocytosed NETs. Once in phagosomes, NETs translocated to the cytosol, where the DNA backbones of these structures activated the innate immune sensor cyclic GMP-AMP synthase (cGAS) and induced type I IFN production. The NET-associated serine protease neutrophil elastase (NE) mediated the activation of this pathway. We showed that NET induction in mice treated with the lectin concanavalin A, a model of autoimmune hepatitis, resulted in cGAS-dependent stimulation of an IFN response, suggesting that NETs activated cGAS in vivo. Thus, our findings suggest that cGAS is a sensor of NETs, mediating immune cell activation during infection.

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 Dates: 2021-03
 Publication Status: Issued
 Pages: -
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 Table of Contents: -
 Rev. Type: -
 Identifiers: DOI: 10.1126/scisignal.aax7942
BibTex Citekey: apel_cytosolic_2021
 Degree: -

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Title: Science Signaling
  Abbreviation : Sci Signal
Source Genre: Journal
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Publ. Info: American Association for the Advancement of Science
Pages: - Volume / Issue: 14 (673) Sequence Number: - Start / End Page: eaax7942 Identifier: ISSN: 1945-0877
CoNE: https://pure.mpg.de/cone/journals/resource/1945-0877