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. 2018 Nov 17;18(6):e41. doi: 10.4110/in.2018.18.e41

Figure 1. Activation of caspase-4/5/11 non-canonical inflammasomes. (A) LPS-harboring OMVs derived from gram-negative bacteria are endocytosed into the host cells, and (B) intracellular LPS directly interacts with mouse caspase-11 or human caspase-4/5 (caspase-4/5/11) through the caspase-4/5/11 CARDs and the lipid A moiety of intracellular LPS, (C) leading to the oligomerization of LPS-caspase-4/5/11 complexes to be activated. (D) Activated caspase 4/5/11 non-canonical inflammasomes cleave the linker loop of GSDMD at Asp276 residue to produce N- and C-terminal GSDMD fragments, and (E) the GSDMD N-terminal fragments generate GSDMD pores in the cell membranes by oligomerization, (F) resulting in cell swelling and rupture, known as pyroptosis. (G) Activated caspase 4/5/11 non-canonical inflammasomes also induce NLRP3 canonical inflammasome activation via an unknown mechanism, (H) leading to the proteolysis and activation of pro-caspase-1 to form active caspase-1 dimers. (I) Active caspase-1 dimer subsequently induces proteolysis and maturation of the inactive pro-inflammatory cytokines pro-IL-1β and pro-IL-18 to active IL-1β and IL-18, and (J) these active IL-1β and IL-18 are secreted through the GSDMD pores.

Figure 1

N, GSDMD N-terminal fragment; C, GSDMD C-terminal fragment; PYD, pyrin domain; NACHT, nucleotide-binding and oligomerization domain; Asp276, aspartic acid 276 residue.