2. Academic Validation
  3. The cytosolic DNA sensor cGAS recognizes neutrophil extracellular traps

The cytosolic DNA sensor cGAS recognizes neutrophil extracellular traps

  • Sci Signal. 2021 Mar 9;14(673):eaax7942. doi: 10.1126/scisignal.aax7942.
Falko Apel 1 2,  Liudmila Andreeva 3 4 5,  Lorenz Sebastian Knackstedt 1 2 6,  Robert Streeck 1 2,  Christian Karl Frese 7,  Christian Goosmann 1 2,  Karl-Peter Hopfner 3,  Arturo Zychlinsky 8 2
Affiliations

Affiliations

  • 1 Max Planck Institute for Infection Biology, Department of Cellular Microbiology, Charitéplatz 1, 10117 Berlin, Germany.
  • 2 Department of Biology, Humboldt University, Charitéplatz 1, 10117 Berlin, Germany.
  • 3 Gene Center, Ludwig-Maximillians-Universität München, Feodor-Lynen-Straße 25, 81377 Munich, Germany.
  • 4 Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
  • 5 Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115, USA.
  • 6 T-Knife GmbH, Robert-Rössle-Straße 10, 13125 Berlin, Germany.
  • 7 Max Planck Unit for the Science of Pathogens, Charitéplatz 1, 10117 Berlin, Germany.
  • 8 Max Planck Institute for Infection Biology, Department of Cellular Microbiology, Charitéplatz 1, 10117 Berlin, Germany. zychlinsky@mpiib-berlin.mpg.de.
PMID: 33688080 DOI: 10.1126/scisignal.aax7942
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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