Functional interplay between non-canonical inflammasomes and autophagy
| Inflammasomes | Functional interplay with autophagy | Models | Ref. |
|---|---|---|---|
| Mouse caspase-11 non-canonical inflammasome | • Detection of GBP-mediated lysed vacuoles by galectin-8 initiated the uptake of gram-negative bacteria into autophagosomes. • Uptake of autophagosome inhibited caspase-11 non-canonical inflammasome activation, which suppressed pyroptosis and secretion of IL-1β in BMDMs. |
Mouse BMDMs | [50] |
| • Caspase-11 deletion prevented HMGB1 release, and caspase-11 activation induced HMGB1 release from autophagy-deficient hepatocytes. • NRF2 is directly bound to the caspase-11 promoter and transcriptionally increases the expression of caspase-11 in hepatocytes. • Autophagy-deficiency-induced NRF2-mediated transcriptional activation of caspase-11 and HMGB1 release from hepatocytes. |
Mouse hepatocytes | [51] | |
| • Deficiency of GABARAP autophagy-related proteins, Gate-16 and Gabarap, induced GBP2-mediated activation of caspase-11 non-canonical inflammasomes, but not canonical inflammasomes, leading to pyroptosis and IL-1β secretion in BMDMs. • Higher mortality was observed in GABARAP autophagy-related protein-deficient mice during LPS-induced lethal sepsis. |
Mouse BMDMs LPS-induced lethal septic mice |
[54] | |
| • Deficiency of Irgm2 aberrantly activated caspase-11 non-canonical inflammasome and caspase-11 non-canonical inflammasome-induced inflammatory responses in BMDMs. • Irgm2-dieificnet mice were more susceptible to caspase-11 non-canonical inflammasome-activated lethal septic shock. |
Mouse BMDMs LPS-induced lethal septic mice |
[58] | |
| • Irgm2/Gate-16 axis cooperatively inhibited caspase-11 non-canonical inflammasome activation and suppressed caspase-11 non-canonical inflammasome-activated pyroptosis and cytokine secretion in BMDMs. • Deficiency of Irgm2 or Gate-16-induced GBP-mediated activation of caspase-11 non-canonical inflammasome. • Irgm2-dieificnet mice were more susceptible to LPS-induced lethal septic shock. |
Mouse BMDMs LPS-induced lethal septic mice |
[59] | |
| • Caspase-11 non-canonical inflammasome promoted • Caspase-11 non-canonical inflammasome promoted fusion of autophagosomes with lysosomes in BMDMs. • Caspase-11-deficient BMDMs exhibited a defect in • Caspase-11 non-canonical inflammasome enhanced the elimination of intracellular |
Mouse BMDMs |
[60] | |
| Human caspase-4 non-canonical inflammasome | • Beclin1 overexpression ameliorated myocardial reperfusion injury in mice by enhancing autophagic flux in human CMECs. • Myocardial ischemia/reperfusion-induced caspase-4 non-canonical inflammasome activation, pyroptosis, and IL-1β secretion in human CMECs and heart of myocardial ischemia/reperfusion mice. • Beclin1 overexpression inhibited caspase-4 non-canonical inflammasome activation, pyroptosis, and IL-1β secretion by promoting autophagic flux in myocardial ischemia/reperfusion mice. • Impaired autophagic flux activated caspase-4 non-canonical inflammasome in human CMECs. • Beclin1 overexpression-driven autophagic flux dampened caspase-4 non-canonical inflammasome activation, pyroptosis, and IL-1β secretion in human CMECs. |
Human CMECs Myocardial ischemia/reperfusion mice |
[62] |
GBP, guanylate‐binding protein; IL, interleukin; BMDMs, bone marrow-derived macrophages; HMGB1, high‐mobility group box 1; LPS, lipopolysaccharide; CMECs, cardiac microvascular endothelial cells.