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dc.contributor.authorBanerjee, Ishita
dc.contributor.authorBehl, Bharat
dc.contributor.authorMendonca, Morena
dc.contributor.authorShrivastava, Gaurav
dc.contributor.authorRusso, Ashley J.
dc.contributor.authorMenoret, Antoine
dc.contributor.authorGhosh, Arundhati
dc.contributor.authorVella, Anthony T.
dc.contributor.authorVanaja, Sivapriya Kailasan.
dc.contributor.authorSarkar, Saumendra N.
dc.contributor.authorFitzgerald, Katherine A.
dc.contributor.authorRathinam, Vijay A. K
dc.date2022-08-11T08:09:10.000
dc.date.accessioned2022-08-23T16:20:04Z
dc.date.available2022-08-23T16:20:04Z
dc.date.issued2018-09-18
dc.date.submitted2020-04-14
dc.identifier.citation<p>Banerjee I, Behl B, Mendonca M, Shrivastava G, Russo AJ, Menoret A, Ghosh A, Vella AT, Vanaja SK, Sarkar SN, Fitzgerald KA, Rathinam VAK. Gasdermin D Restrains Type I Interferon Response to Cytosolic DNA by Disrupting Ionic Homeostasis. Immunity. 2018 Sep 18;49(3):413-426.e5. doi: 10.1016/j.immuni.2018.07.006. Epub 2018 Aug 28. PMID: 30170814; PMCID: PMC6347470. <a href="https://doi.org/10.1016/j.immuni.2018.07.006">Link to article on publisher's site</a></p>
dc.identifier.issn1074-7613 (Linking)
dc.identifier.doi10.1016/j.immuni.2018.07.006
dc.identifier.pmid30170814
dc.identifier.urihttp://hdl.handle.net/20.500.14038/35197
dc.description.abstractInflammasome-activated caspase-1 cleaves gasdermin D to unmask its pore-forming activity, the predominant consequence of which is pyroptosis. Here, we report an additional biological role for gasdermin D in limiting cytosolic DNA surveillance. Cytosolic DNA is sensed by Aim2 and cyclic GMP-AMP synthase (cGAS) leading to inflammasome and type I interferon responses, respectively. We found that gasdermin D activated by the Aim2 inflammasome suppressed cGAS-driven type I interferon response to cytosolic DNA and Francisella novicida in macrophages. Similarly, interferon-beta (IFN-beta) response to F. novicida infection was elevated in gasdermin D-deficient mice. Gasdermin D-mediated negative regulation of IFN-beta occurred in a pyroptosis-, interleukin-1 (IL-1)-, and IL-18-independent manner. Mechanistically, gasdermin D depleted intracellular potassium (K(+)) via membrane pores, and this K(+) efflux was necessary and sufficient to inhibit cGAS-dependent IFN-beta response. Thus, our findings have uncovered an additional interferon regulatory module involving gasdermin D and K(+) efflux.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=30170814&dopt=Abstract">Link to Article in PubMed</a></p>
dc.relation.urlhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6347470/
dc.subjectImmunology and Infectious Disease
dc.titleGasdermin D Restrains Type I Interferon Response to Cytosolic DNA by Disrupting Ionic Homeostasis
dc.typeJournal Article
dc.source.journaltitleImmunity
dc.source.volume49
dc.source.issue3
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/infdis_pp/422
dc.identifier.contextkey17361283
html.description.abstract<p>Inflammasome-activated caspase-1 cleaves gasdermin D to unmask its pore-forming activity, the predominant consequence of which is pyroptosis. Here, we report an additional biological role for gasdermin D in limiting cytosolic DNA surveillance. Cytosolic DNA is sensed by Aim2 and cyclic GMP-AMP synthase (cGAS) leading to inflammasome and type I interferon responses, respectively. We found that gasdermin D activated by the Aim2 inflammasome suppressed cGAS-driven type I interferon response to cytosolic DNA and Francisella novicida in macrophages. Similarly, interferon-beta (IFN-beta) response to F. novicida infection was elevated in gasdermin D-deficient mice. Gasdermin D-mediated negative regulation of IFN-beta occurred in a pyroptosis-, interleukin-1 (IL-1)-, and IL-18-independent manner. Mechanistically, gasdermin D depleted intracellular potassium (K(+)) via membrane pores, and this K(+) efflux was necessary and sufficient to inhibit cGAS-dependent IFN-beta response. Thus, our findings have uncovered an additional interferon regulatory module involving gasdermin D and K(+) efflux.</p>
dc.identifier.submissionpathinfdis_pp/422
dc.contributor.departmentDepartment of Medicine, Division of Infectious Diseases and Immunology
dc.source.pages413-426.e5


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