Dangerous Liaisons: Mitochondrial DNA Meets the NLRP3 Inflammasome

Danger signals released by damaged organelles can promote inflammation. In this issue of Immunity, Shimada et al. (2012) report that oxidized DNA, released by mitochondria, directly binds and activates the NLRP3 inflammasome

Inflammatory Caspases Linking an Intracellular Innate Immune System to Autoinflammatory Diseases

AbstractCaspases not only play an essential role during apoptotic cell death, but a subfamily of them—the inflammatory caspases—are associated with immune responses to microbial pathogens. Activation of inflammatory caspases, such as caspase-1 and caspase-5, occurs upon assembly of an intracellular complex, designated the inflammasome. This results in the cleavage and activation of the proinflammatory cytokines IL-1β and IL-18. Mutations in one of the scaffold proteins of the inflammasome, NALP3/Cryopyrin, are associated with autoinflammatory disorders underscoring the importance of regulating inflammatory caspase activation

Linking Inflammasome Activation and Phagosome Maturation

SummaryOne-third of the world's population is infected with Mycobacterium tuberculosis, one of the most effective human pathogens, whose success is attributed to the deployment of remarkably sophisticated immune evasion mechanisms. In this issue of Cell Host & Microbe, a new study unravels a novel strategy of immune evasion and enhanced bacterial intracellular survival, which is dependent on inhibition of inflammasome activation by an M. tuberculosis-encoded metalloprotease

Cell-Free Assay for Inflammasome Activation

International audienceInflammasomes are multiprotein complexes, which assembly results in caspase-1 activation and subsequent IL-1β and IL-18 activation and secretion. In a cell-free system, based on cytosols of normally growing cells, the disruption of the cell membrane spontaneously activates the inflammasome. Studying the activation of the inflammasome in cytosolic extracts provides multiple advantages, as it is synchronized, rapid, strong, and mostly plasma membrane-free. This protocol covers the methods required to prepare cell lysates and study inflammasome activation using different read-outs. General considerations are provided that may help in the design of modified methods. This assay can be useful to study potential inflammasome interactors and the signaling pathways involved in its activation

Inflammatory Diseases: Is Ubiquitinated NEMO at the Hub?

AbstractMany patients with Crohn's disease carry mutations in NOD2, a molecule that can both activate and attenuate the pro-inflammatory effects of NF-κB. Recent studies implicate NOD2-induced ubiquitination of the NF-κB regulator NEMO as a potential means of manipulating the NF-κB signal

Pyroptosis: Caspase-11 Unlocks the Gates of Death

How inflammatory caspases trigger pyroptotic cell death is mostly unexplained. In this issue of Immunity, Núñez and colleagues report that caspase-11 cleaves the transmembrane channel pannexin-1, causing an efflux of cellular ATP that promotes a P2X7 receptor-dependent pyroptosis