Regulation of inflammasome signaling

Regulation of inflammasome signaling

19 March 2012 | Vijay A K Rathinam, Sivapriya Kailasan Vanaja & Katherine A Fitzgerald
The regulation of inflammasome signaling is crucial for maintaining immunological balance and preventing sterile inflammation. Inflammasomes, which include NLR and PYHIN families, play a central role in the innate immune response by regulating the production of pro-inflammatory cytokines such as interleukin 1β (IL-1β) and IL-18, and promoting pyroptosis. The activation of inflammasomes involves the recognition of microbial products or endogenous molecules released from damaged or dying cells, leading to the recruitment and activation of caspase-1. Caspase-1 then processes IL-1β and IL-18, and promotes pyroptosis. The NLRP3 inflammasome is the best-studied member, activated by a wide range of signals, including pathogens, endogenous danger signals, and environmental triggers. The NLRC4 inflammasome responds to bacterial flagellin and Prg1, while the NLRP1 inflammasome is activated by anthrax lethal toxin. The NLRP6 and NLRP12 inflammasomes have additional roles in maintaining intestinal homeostasis and regulating the microbiome. Pyrin-only and CARD-only proteins (POPs and COPs) also play key roles in regulating inflammasome activity. Microbial pathogens have evolved strategies to evade inflammasome activation, such as producing serpin-like molecules that inhibit caspase-1 activity. Type I interferons can both enhance and antagonize inflammasome responses, depending on the cell type and the specific pathway involved. Autophagy, a catabolic process, regulates IL-1β production by sequestering damaged mitochondria and targeting pro-IL-1β for degradation. The TRIM family of proteins also modulates inflammasome-mediated IL-1 responses. Understanding the complex regulatory mechanisms of inflammasomes is essential for developing treatments for infectious and inflammatory diseases.The regulation of inflammasome signaling is crucial for maintaining immunological balance and preventing sterile inflammation. Inflammasomes, which include NLR and PYHIN families, play a central role in the innate immune response by regulating the production of pro-inflammatory cytokines such as interleukin 1β (IL-1β) and IL-18, and promoting pyroptosis. The activation of inflammasomes involves the recognition of microbial products or endogenous molecules released from damaged or dying cells, leading to the recruitment and activation of caspase-1. Caspase-1 then processes IL-1β and IL-18, and promotes pyroptosis. The NLRP3 inflammasome is the best-studied member, activated by a wide range of signals, including pathogens, endogenous danger signals, and environmental triggers. The NLRC4 inflammasome responds to bacterial flagellin and Prg1, while the NLRP1 inflammasome is activated by anthrax lethal toxin. The NLRP6 and NLRP12 inflammasomes have additional roles in maintaining intestinal homeostasis and regulating the microbiome. Pyrin-only and CARD-only proteins (POPs and COPs) also play key roles in regulating inflammasome activity. Microbial pathogens have evolved strategies to evade inflammasome activation, such as producing serpin-like molecules that inhibit caspase-1 activity. Type I interferons can both enhance and antagonize inflammasome responses, depending on the cell type and the specific pathway involved. Autophagy, a catabolic process, regulates IL-1β production by sequestering damaged mitochondria and targeting pro-IL-1β for degradation. The TRIM family of proteins also modulates inflammasome-mediated IL-1 responses. Understanding the complex regulatory mechanisms of inflammasomes is essential for developing treatments for infectious and inflammatory diseases.
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