page_title: Inflammasome
hierarchical_section_title: Inflammasome
caption_attribution_description: English: Inflammasome, a multiprotein complex that mediates the activation of Caspase-1. Dysregulation of inflammasomes has also been linked to a number of autoinflammatory and autoimmune disorders.
context_page_description: Inflammasomes are cytosolic multiprotein oligomers of the innate immune system responsible for the activation of inflammatory responses. Activation and assembly of the inflammasome promotes proteolytic cleavage, maturation and secretion of pro-inflammatory cytokines interleukin 1β and interleukin 18, as well as cleavage of Gasdermin-D. The N-terminal fragment resulting from this cleavage induces a pro-inflammatory form of programmed cell death distinct from apoptosis, referred to as pyroptosis, and is responsible for secretion of the mature cytokines, presumably through the formation of pores in the plasma membrane. In the case of dysregulation of inflammasome activation, an assortment of major diseases, such as cancer, autoimmune, metabolic and neurodegenerative diseases may arise.
  Traditionally, inflammasomes have mainly been studied in professional immune cells of the innate immune system, such as macrophages. More recent studies, however, indicate high levels of inflammasome component expression in epithelial barrier tissues, where they have been shown represent an important first line of defense.
context_section_description: Inflammasomes are cytosolic multiprotein oligomers  of the innate immune system responsible for the activation of inflammatory responses. Activation and assembly of the inflammasome promotes proteolytic cleavage, maturation and secretion of pro-inflammatory cytokines interleukin 1β (IL-1β) and interleukin 18 (IL-18), as well as cleavage of Gasdermin-D. The N-terminal fragment resulting from this cleavage induces a pro-inflammatory form of programmed cell death distinct from apoptosis, referred to as pyroptosis,  and is responsible for secretion of the mature cytokines, presumably through the formation of pores in the plasma membrane. In the case of dysregulation of inflammasome activation, an assortment of major diseases, such as cancer, autoimmune, metabolic and neurodegenerative diseases may arise.
  Traditionally, inflammasomes have mainly been studied in professional immune cells of the innate immune system, such as macrophages. More recent studies, however, indicate high levels of inflammasome component expression in epithelial barrier tissues, where they have been shown represent an important first line of defense. Inflammasome activation is initiated by different kinds of cytosolic pattern recognition receptors (PRRs) that respond to either microbe-derived pathogen-associated molecular patterns (PAMPs) or danger-associated molecular patterns (DAMPs) generated by the host cell. Pattern recognition receptors involved in inflammasomes comprise NLRs (nucleotide-binding oligomerization domain and leucine-rich repeat-containing receptors) as well as AIM2 (absent in melanoma 2), IFI16 (IFN-inducible protein 16 ) as well as pyrin. 
  Through their caspase activation and recruitment domain (CARD) or pyrin domain (PYD), the inflammasome receptors interact with the adaptor protein ASC, which then recruits pro-caspase-1 via its CARD domain and activates the effector caspase through proteolytic cleavage. The activated caspase-1 finally cleaves the immature pro-inflammatory cytokines pro-IL-1β and pro-IL-18, as well as Gasdermin-D, which are responsible for inflammatory signaling and pyroptotic cell death, respectively. In addition to these so-called canonical inflammasomes, different studies also described non-canonical inflammasome complexes that act independently of caspase-1. In mice, the non-canonical inflammasome is activated by direct sensing of cytosolic bacterial lipopolysaccharide (LPS) by caspase-11, which subsequently induces pyroptotic cell death. In human cells, the corresponding caspases of the non-canonical inflammasome are caspase 4 and caspase 5.
caption: Inflammasome structure
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