| First Author | Banerjee I | Year | 2018 |
| Journal | Immunity | Volume | 49 |
| Issue | 3 | Pages | 413-426.e5 |
| PubMed ID | 30170814 | Mgi Jnum | J:277997 |
| Mgi Id | MGI:6284424 | Doi | 10.1016/j.immuni.2018.07.006 |
| Citation | Banerjee I, et al. (2018) Gasdermin D Restrains Type I Interferon Response to Cytosolic DNA by Disrupting Ionic Homeostasis. Immunity 49(3):413-426.e5 |
| abstractText | 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. |
