title: Caspase-1-induced pyroptotic cell death.
abstract: Programmed cell death is a necessary part of development and tissue homeostasis enabling the removal of unwanted cells. In the setting of infectious disease, cells that have been commandeered by microbial pathogens become detrimental to the host. When macrophages and dendritic cells are compromised in this way, they can be lysed by pyroptosis, a cell death mechanism that is distinct from apoptosis and oncosis/necrosis. Pyroptosis is triggered by Caspase-1 after its activation by various inflammasomes and results in lysis of the affected cell. Both pyroptosis and apoptosis are programmed cell death mechanisms but are dependent on different caspases, unlike oncosis. Similar to oncosis and unlike apoptosis, pyroptosis results in cellular lysis and release of the cytosolic contents to the extracellular space. This event is predicted to be inherently inflammatory and coincides with interleukin-1β (IL-1β) and IL-18 secretion. We discuss the role of distinct inflammasomes, including NLRC4, NLRP3, and AIM2, as well as the role of the ASC focus in Caspase-1 signaling. We further review the importance of pyroptosis in vivo as a potent mechanism to clear intracellular pathogens.
authors: Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. edmiao1@gmail.com
authors: Edward A
authors: EA
authors: Miao
authors: Jayant V
authors: JV
authors: Rajan
authors: Alan
authors: A
authors: Aderem
mesh_terms: D000818:Animals; D053468:CARD Signaling Adaptor Proteins / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D020170:Caspase 1 / Q000276:immunology* / Q000378:metabolism; D016923:Cell Death / Q000276:immunology; D004268:DNA-Binding Proteins; D003713:Dendritic Cells / Q000276:immunology* / Q000382:microbiology / Q000821:virology; D006801:Humans; D017053:Infection Control; D007239:Infections / Q000276:immunology*; D058847:Inflammasomes / Q000276:immunology*; D020382:Interleukin-18 / Q000276:immunology; D053583:Interleukin-1beta / Q000276:immunology; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology / Q000821:virology; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D009687:Nuclear Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology
chemical_list: C410167:AIM2 protein, human; D053468:CARD Signaling Adaptor Proteins; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D058847:Inflammasomes; D020382:Interleukin-18; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C435692:NLRC4 protein, human; C453881:NLRP3 protein, human; D009687:Nuclear Proteins; D020170:Caspase 1