Skip to main content
. 2021 Jul 15;22(14):7580. doi: 10.3390/ijms22147580

Figure 4.

Figure 4

Inflammasome-activated inflammatory signaling (A) the domain structure of PRRs. Inflammasome PRRs are intracellular sensors that include PYD and/or CARD. The PRRs also include NACHT, LRRs, and FIIND in NLR family members. Pyrin includes Bbox, CC, and B30.2 and AIM2 includes HIN200. Caspase-4/5/11 have the same domain structure that includes CARD, p20, and p10. *Absence in mouse NLRP1 isoforms (B) The structure of inflammasomes. Inflammasome PRRs that include a PYD, such as human NLRP1, NLRP3, NLRP6, NLRP9, pyrin, and AIM2 recruit a bipartite adaptor, ASC to mediate CARD-CARD interactions with pro-caspase-1 (ASC-positive scaffolds). While inflammasome PRRs that include CARD instead of PYD, such as mouse NLRP1b and NLRC4 interact directly with pro-caspase-1 without the help of ASC (ASC-negative scaffolds). PRRs of non-canonical inflammasomes, such as mouse caspase-11, human caspase-4, and caspase-5 that include CARD sense directly intracellular LPS and mediate CARD–CARD interaction without the binding of ASC and pro-caspase-1. (C) Inflammasome-activated inflammatory signaling pathways. Inflammasomes are activated in response to PAMPs and DAMPs. The PRRs of canonical inflammasomes directly interact with their specific ligands and respond to various cellular danger signals. The canonical inflammasomes activate caspase-1 by the proteolytic cleavage of CARD and produce active caspase-1 dimers. Activated caspase-1 induces proteolytic cleavage of GSDMD to generate N-GSDMD that then generates GSDMD pores and induces pyroptosis. Activated caspase-1 also induces proteolytic maturation of IL-1β and IL-18 into their active forms, which are secreted through GSDMD pores. PRRs of non-canonical inflammasomes (mouse caspase-11, human caspase-4, and caspase-5) directly interact with intracellular LPS derived from Gram-negative bacteria. The activation of non-canonical inflammasomes also induces proteolytic cleavage of GSDMD, leading to pyroptosis. Non-canonical inflammasomes activate NLRP3 canonical inflammasome by facilitating K+ efflux, which subsequently induces proteolytic maturation and secretion of IL-1β and IL-18 through GSDMD pores. PYD, pyrin domain; CARD, caspase recruitment domain; NACHT, nucleotide-binding and oligomerization domain, LRRs, leucine-rich repeats, FIIND, a functional-to-find domain; Bbox, B-box-type zinc finger; CC, coiled-coil; AIM2, absent in melanoma 2; HIN200, hematopoietic interferon-inducible nuclear protein 200; ASC, apoptosis-associated speck-like protein containing a caspase recruitment domain; GSDMD, gasdermin D; LPS, lipopolysaccharide.