Some PRRs can induce the formation of a multiprotein complex called the inflammasome that leads to the processing and release of the proinflammatory cytokines IL-1β and IL-18 and cell death in the form of pyroptosis.
First-pass extracted concept
inflammasome
Candidate: concept label1 source documents11 linked claims
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NLRP1, NLRP3, NLRC4, AIM2, and pyrin are described as well-characterized intracellular receptors that form inflammasomes, whereas NLRC1 and NLRC2 are described as NLR family members that do not.
AIM2 is described as a nucleic acid sensor that responds to diverse pathogens, and IRF1-induced GBPs and IRGB10 can rupture bacteria to release ligands sensed by AIM2 and the noncanonical NLRP3 inflammasome.
NLRC4 activation requires NAIP proteins that provide ligand specificity for flagellin and type III secretion system proteins from many Gram-negative bacteria.
NLRP1 contains a FIIND domain that undergoes autoproteolysis, and its activation requires proteasome-mediated degradation of the N-terminus to free the C-terminal region for inflammasome formation.
Noncanonical NLRP3 activation can be driven by caspase-11 in mice and caspase-4/5 in humans after sensing cytoplasmic LPS, leading to gasdermin D cleavage, pyroptosis, and ion changes that trigger NLRP3 inflammasome activation.
Pyrin does not directly sense pathogens but responds to RhoA inactivation; under homeostatic conditions pyrin is restrained by RhoA-activated kinase phosphorylation and 14-3-3 binding, whereas bacterial Rho inactivation releases this inhibition and permits inflammasome formation.
Some intracellular pattern recognition receptors form inflammasomes that activate caspase-1, process IL-1β and IL-18, and drive pyroptotic cell death.
ZBP1 is described as the innate immune sensor that triggers NLRP3 activation during influenza A virus infection through sensing Z-nucleic acids, and deletion of the Zα2 sensing domain abolishes this NLRP3 activation response.
ZBP1 is involved in formation of both the ZBP1-NLRP3 inflammasome and the ZBP1 PANoptosome, and these are described as critical for host defense during influenza A virus infection.
The article describes NLRP3 inflammasome activation as protective in some infectious settings but also capable of causing pathological inflammation, with conflicting protective and pathogenic roles reported in leishmaniasis.
Inflammasome pathway components including IL-1β, IL-18, caspase-1, gasdermin D, and NLRP3 are described as targets for therapeutic modulation, with canakinumab cited as an approved anti-IL-1β therapy for CAPS that was also reported to reduce cardiovascular events, mortality, and lung cancer incidence in CANTOS.