Figure 4. Inhibitory effects of NAD⁺ on IFN-β downstream signaling and inflammasome activation.

NAD⁺ inhibits signal transducer activator of transcription-1 (STAT-1) expression and phosphorylation, thus compromising the intracellular response to IFN-β. Subsequently, stimulation of the IFNAR receptor by IFN-β leads to a decreased transcription of pro-caspase-11 as well as IFN-stimulated genes (ISGs) (IFN-inducible GTPases and GBPs). Due to diminished caspase-11 levels, non-canonical inflammasome activation through intracellular, gram-negative bacteria opsonization by GBPs is significantly inhibited.