Cell biology of inflammasome activation

Inflammasome components are expressed in immune and nonimmune cells, contributing to sensing of pathogens and danger signals, triggering inflammation and cell death, and shaping the development of infectious diseases, autoimmunity, cancer, and metabolic diseases. Inflammasome sensors trigger inflammasome-dependent and/or inflammasome-independent functions in different mammalian cells. Cellular organelles such as mitochondria, endoplasmic reticulum, Golgi apparatus, nucleus, microtubule-organizing center, and even the pathogen surface, act as platforms for trafficking and assembly of inflammasome complexes. Inflammasome-mediated, gasdermin-D-dependent, pyroptotic cell death is an active cellular process, requiring the plasma membrane disruptor ninjurin-1. Organelles are critical structures in mediating the assembly and activation of inflammasomes in mammalian cells, resulting in inflammation and cell death. Assembly of inflammasomes can occur at the mitochondria, endoplasmic reticulum, nucleus, trans-Golgi network, or pathogen surface, facilitated by the overarching architecture of the cytoskeleton. NLRP3 and Pyrin inflammasome sensors may form smaller speckles and converge on a single larger speck at the microtubule-organizing center (MTOC). This signaling hub activates multiple mammalian inflammatory and apoptotic caspases, cytokine substrates, the pore-forming protein gasdermin D, and the plasma membrane rupture protein ninjurin-1 (NINJ1), allowing pyroptosis, cellular disintegration, and inflammation to ensue. In this review, we highlight the role of mammalian cell types and organellar architectures in executing inflammasome responses. Organelles are critical structures in mediating the assembly and activation of inflammasomes in mammalian cells, resulting in inflammation and cell death. Assembly of inflammasomes can occur at the mitochondria, endoplasmic reticulum, nucleus, trans-Golgi network, or pathogen surface, facilitated by the overarching architecture of the cytoskeleton. NLRP3 and Pyrin inflammasome sensors may form smaller speckles and converge on a single larger speck at the microtubule-organizing center (MTOC). This signaling hub activates multiple mammalian inflammatory and apoptotic caspases, cytokine substrates, the pore-forming protein gasdermin D, and the plasma membrane rupture protein ninjurin-1 (NINJ1), allowing pyroptosis, cellular disintegration, and inflammation to ensue. In this review, we highlight the role of mammalian cell types and organellar architectures in executing inflammasome responses. an intracellular signaling pathway regulating cell cycle, leading to cell proliferation. a noninflammatory form of programmed cell death mediated by apoptotic caspases and characterized by membrane blebbing, DNA fragmentation, and cell shrinkage. double-membraned vesicles that contain cellular material to be degraded by autophagy. membrane-bound organelles that act as reservoirs for digestive enzymes and antimicrobial proteins, including myeloperoxidase, α-defensins, elastase, proteinase-3, and cathepsin G. a family of enzymes with a central role in programmed cell death pathways, including pyroptosis, by processing their substrates at specific aspartate residues. a condition of having imbalances in the microbial communities of the gastrointestinal tract or other parts of the body. Dysbiosis in the intestine has been linked to diseases such as inflammatory bowel disease. a hematopoietic growth factor responsible for promoting proliferation and differentiation of stem cells into granulocytes (neutrophils, eosinophils, and basophils), macrophages, and dendritic cells. a non-histone nuclear protein released during cell injury or cell death. a hydrogen transfer enzyme found in the cytoplasm of most cells and released during cell injury or cell death. a cellular structure composed of two orthogonally arranged centrioles and pericentriolar material, which nucleates and anchors microtubules. a dynamic cellular connection between the subdomain of the endoplasmic reticulum and the outer mitochondrial membrane. MAMs are involved in mediating autophagy, Ca2+ transport, and lipid metabolism. a form of autophagy that selectively degrades damaged mitochondria. a form of inflammatory cell death that can be activated by ligands of death receptors and stimuli that induce the expression of death receptor ligands under certain conditions. web-like chromatin-protein structures released into the extracellular space during neutrophil cell death; used to capture microbes, promote coagulation, and activate myeloid cells. a homophilic cell adhesion molecule induced, in some cases, by nerve injury. NINJ1 mediates plasma membrane rupture following programmed cell death pathways. a family of fatty acid eicosanoids synthesized from arachidonic acid via cyclooxygenase, an enzyme involved in the synthesis of prostaglandins, prostacyclin, and thromboxane, and the target of anti-inflammatory drugs such as ibuprofen. a major secretory pathway and sorting station that directs newly synthesized proteins to different subcellular destinations.