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Gasdermin D Restrains Type I Interferon Response to Cytosolic DNA by Disrupting Ionic Homeostasis.
- Source :
-
Immunity (10747613) . Sep2018, Vol. 49 Issue 3, p413-413. 1p. - Publication Year :
- 2018
-
Abstract
- Summary 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-β (IFN-β) response to F. novicida infection was elevated in gasdermin D-deficient mice. Gasdermin D-mediated negative regulation of IFN-β 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-β response. Thus, our findings have uncovered an additional interferon regulatory module involving gasdermin D and K+ efflux. Graphical Abstract Highlights • Inflammasome-activated gasdermin D limits type I interferon responses to cytosolic DNA • Gasdermin D targets cGAS activation to inhibit IFN-β response to cytosolic DNA • Depletion of intracellular K+ by gasdermin D is responsible for limiting cGAS signaling • K+ efflux is sufficient to inhibit cGAS-dependent type I interferon responses Gasdermin D is a pore-forming protein, which upon activation by inflammasome complexes mediates pyroptotic cell death and IL-1 release. Banerjee et al. demonstrate a previously unknown regulatory role for gasdermin D-driven K+ efflux in reining in cGAS-dependent type I interferon response to cytosolic DNA. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 10747613
- Volume :
- 49
- Issue :
- 3
- Database :
- Academic Search Index
- Journal :
- Immunity (10747613)
- Publication Type :
- Academic Journal
- Accession number :
- 131766847
- Full Text :
- https://doi.org/10.1016/j.immuni.2018.07.006