Inflammasomes are multiprotein complexes within the cytoplasm of immune cells that play a critical role in the innate immune response by promoting inflammation. These complexes are primarily formed in response to pathogenic microorganisms and stress signals, leading to the activation of pro-inflammatory cytokines.
The assembly of inflammasomes is initiated by pattern recognition receptors (PRRs) such as NOD-like receptors (NLRs) and AIM2-like receptors (ALRs). Upon detecting pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs), these receptors oligomerize and recruit the adaptor protein ASC (apoptosis-associated speck-like protein containing a CARD). ASC, in turn, recruits and activates pro-caspase-1, an inactive precursor of the enzyme caspase-1.
Once activated, caspase-1 cleaves pro-inflammatory cytokines, such as pro-interleukin-1β (pro-IL-1β) and pro-interleukin-18 (pro-IL-18), into their active forms, IL-1β and IL-18. These cytokines are then secreted from the cell, leading to the recruitment of immune cells to the site of infection or injury, thus amplifying the inflammatory response. Additionally, caspase-1 activation can induce a form of programmed cell death known as pyroptosis, which further helps to contain and eliminate the pathogen.
Inflammasomes play a crucial role in host defense but must be tightly regulated to prevent excessive inflammation, which can lead to chronic inflammatory diseases and tissue damage. Dysregulation of inflammasome activity has been implicated in a variety of conditions, including autoimmune diseases, metabolic disorders, and neurodegenerative diseases.