期刊
IMMUNITY
卷 49, 期 3, 页码 413-+出版社
CELL PRESS
DOI: 10.1016/j.immuni.2018.07.006
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-
类别
资金
- NIH [AI119015, AI083713, AI118896]
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+) viamembrane 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.
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