Cryopyrin and pyrin activate caspase-1, but not NF-kappaB, via ASC oligomerization 2006
The different NOD-like receptors (NLRs) involved in inflammasome assembly in a stimulus-dependent fashion are shown. a | When NALP3 (NACHT-, LRR- and pyrin-domain-containing protein 3) is activated by inflammasome inducers (such as potassium efflux-inducing agents, bacteria, toxins, bacterial RNA, gout crystals and trinitrophenylchloride (TNP)), a complex composed of NALP3, ASC (apoptosis-associated speck-like protein containing a CARD) and caspase-1 assembles, thereby activating caspase-1. b | Anthrax lethal toxin seems to activate NALP1b in mouse macrophages and perhaps uses ASC to recruit and activate caspase-1. c | Francisella tularensis replication in the cytosol is detected by an unidentified NLR, which recruits ASC and caspase-1. d,e | Intracellular Legionella pneumophila (d) and Salmonella typhimurium (e) are sensed by IPAF (ICE-protease activating factor) and NAIP5 (neuronal apoptosis inhibitor protein 5) for L. pneumophila and perhaps an additional NLR for S. typhimurium by a mechanism that might involve the detection of monomeric flagellin in the cytosol. The two versions of inflammasome assembly and activation for infections with L. pneumophila and S. typhimurium reflect the ability of ASC to nucleate assembly early on, but could be dispensable later during infection or in the presence of high numbers of bacteria. IL-1beta, interleukin-1beta; TLR, Toll-like receptor.
Inflammasome adaptors and sensors: intracellular regulators of infection and inflammation 2007
Cathelicidin peptide LL-37 inhibits AIM2 inflammasome activation in keratinocytes in psoriasis by neutralizing cytosolic self-DNA. In psoriatic plaques, DNA is found in the cytosol of keratinocytes, which triggers AIM2 inflammasome activation (as displayed in TUNEL stainings on the right panel). The source of the DNA remains unknown: Whether this detected DNA is exogenous and taken up from dying cells in the epidermis or endogenous, for example, leaking from damaged nuclei or mitochondria is unknown (marked by ‘?’). LL-37 that is increased by topical treatment with vitamin D analogues or UVB treatment binds to cytosolic self-DNA and neutralizes the activating effect of DNA on the AIM2 inflammasome – thereby blocking IL-1β release.