دورية أكاديمية

The cytosolic DNA sensor cGAS recognizes neutrophil extracellular traps.

التفاصيل البيبلوغرافية
العنوان: The cytosolic DNA sensor cGAS recognizes neutrophil extracellular traps.
المؤلفون: Apel F; Max Planck Institute for Infection Biology, Department of Cellular Microbiology, Charitéplatz 1, 10117 Berlin, Germany.; Department of Biology, Humboldt University, Charitéplatz 1, 10117 Berlin, Germany., Andreeva L; Gene Center, Ludwig-Maximillians-Universität München, Feodor-Lynen-Straße 25, 81377 Munich, Germany.; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115, USA., Knackstedt LS; Max Planck Institute for Infection Biology, Department of Cellular Microbiology, Charitéplatz 1, 10117 Berlin, Germany.; Department of Biology, Humboldt University, Charitéplatz 1, 10117 Berlin, Germany.; T-Knife GmbH, Robert-Rössle-Straße 10, 13125 Berlin, Germany., Streeck R; Max Planck Institute for Infection Biology, Department of Cellular Microbiology, Charitéplatz 1, 10117 Berlin, Germany.; Department of Biology, Humboldt University, Charitéplatz 1, 10117 Berlin, Germany., Frese CK; Max Planck Unit for the Science of Pathogens, Charitéplatz 1, 10117 Berlin, Germany., Goosmann C; Max Planck Institute for Infection Biology, Department of Cellular Microbiology, Charitéplatz 1, 10117 Berlin, Germany.; Department of Biology, Humboldt University, Charitéplatz 1, 10117 Berlin, Germany., Hopfner KP; Gene Center, Ludwig-Maximillians-Universität München, Feodor-Lynen-Straße 25, 81377 Munich, Germany., Zychlinsky A; Max Planck Institute for Infection Biology, Department of Cellular Microbiology, Charitéplatz 1, 10117 Berlin, Germany. zychlinsky@mpiib-berlin.mpg.de.; Department of Biology, Humboldt University, Charitéplatz 1, 10117 Berlin, Germany.
المصدر: Science signaling [Sci Signal] 2021 Mar 09; Vol. 14 (673). Date of Electronic Publication: 2021 Mar 09.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: American Association for the Advancement of Science Country of Publication: United States NLM ID: 101465400 Publication Model: Electronic Cited Medium: Internet ISSN: 1937-9145 (Electronic) Linking ISSN: 19450877 NLM ISO Abbreviation: Sci Signal Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Washington, D.C. : American Association for the Advancement of Science
مواضيع طبية MeSH: Extracellular Traps*, Animals ; Cytosol ; DNA ; Mice ; Neutrophils ; Nucleotidyltransferases/genetics
مستخلص: 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.
(Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
المشرفين على المادة: 9007-49-2 (DNA)
EC 2.7.7.- (Nucleotidyltransferases)
تواريخ الأحداث: Date Created: 20210310 Date Completed: 20220113 Latest Revision: 20220113
رمز التحديث: 20240628
DOI: 10.1126/scisignal.aax7942
PMID: 33688080
قاعدة البيانات: MEDLINE
الوصف
تدمد:1937-9145
DOI:10.1126/scisignal.aax7942