Banerjee, IshitaBehl, BharatMendonca, MorenaShrivastava, GauravRusso, Ashley J.Menoret, AntoineGhosh, ArundhatiVella, Anthony T.Vanaja, Sivapriya Kailasan.Sarkar, Saumendra N.Fitzgerald, Katherine ARathinam, Vijay A. K2022-08-232022-08-232018-09-182020-04-14<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>1074-7613 (Linking)10.1016/j.immuni.2018.07.00630170814https://hdl.handle.net/20.500.14038/35197Inflammasome-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.en-USImmunology and Infectious DiseaseJournal Articlehttps://escholarship.umassmed.edu/infdis_pp/42217361283infdis_pp/422