摘要：SummaryIn mammalian cells, inflammatory caspases detect Gram-negative bacterial invasion by binding lipopolysaccharides (LPS). Murine caspase-11 binds cytosolic LPS, stimulates pyroptotic cell death, and drives sepsis pathogenesis. Extracellular priming factors enhance caspase-11-dependent pyroptosis. Herein we compare priming agents and demonstrate that IFNγpriming elicits the most rapid and amplified macrophage response to cytosolic LPS. Previous studies indicate that IFN-induced expression of caspase-11 and guanylate binding proteins (GBPs) are causal events explaining the effects of priming on cytosolic LPS sensing. We demonstrate that these events cannot fully account for the increased response triggered by IFNγtreatment. Indeed, IFNγpriming elicits higher pyroptosis levels in response to cytosolic LPS when macrophages stably express caspase-11. In macrophages lacking GBPs encoded on chromosome 3, IFNγpriming enhanced pyroptosis in response to cytosolic LPS as compared with other priming agents. These results suggest an unknown regulator of caspase-11-dependent pyroptosis exists, whose activity is upregulated by IFNγ.Graphical AbstractDisplay OmittedHighlights•IFNγpriming elicits the most rapid and amplified response to cytosolic LPS•The enhanced IFNγ-triggered response is separable from CASP11 expression•The enhanced IFNγ-triggered response is independent of GBPs encoded on chromosome 3•We propose an unknown IFNγ-induced regulator of CASP11-dependent pyroptosis existsImmunology; Cell Biology
