Activation and regulation of the inflammasomes
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TLDR
The complex regulatory mechanisms that facilitate a balanced but effective inflammasome-mediated immune response are discussed, and the similarities to another molecular signalling platform — the apoptosome — that monitors cellular health are highlighted.Abstract:
Inflammasomes are key signalling platforms that detect pathogenic microorganisms and sterile stressors, and that activate the highly pro-inflammatory cytokines interleukin-1β (IL-1β) and IL-18. In this Review, we discuss the complex regulatory mechanisms that facilitate a balanced but effective inflammasome-mediated immune response, and we highlight the similarities to another molecular signalling platform - the apoptosome - that monitors cellular health. Extracellular regulatory mechanisms are discussed, as well as the intracellular control of inflammasome assembly, for example, via ion fluxes, free radicals and autophagy.read more
Citations
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Inflammasomes: mechanism of assembly, regulation and signalling
Petr Broz,Vishva M. Dixit +1 more
TL;DR: This Review discusses the recent developments in inflammasome research with a focus on the molecular mechanisms that govern inflammaome assembly, signalling and regulation.
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A small-molecule inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases
Rebecca C. Coll,Avril A. B. Robertson,Jae Jin Chae,Sarah C. Higgins,Raúl Muñoz-Planillo,Marco Inserra,Irina Vetter,Lara S. Dungan,Brian G. Monks,Andrea Stutz,Daniel E. Croker,Mark S. Butler,Moritz Haneklaus,Caroline E. Sutton,Gabriel Núñez,Eicke Latz,Daniel L. Kastner,Kingston H. G. Mills,Seth L. Masters,Kate Schroder,Mark E. Cooper,Luke A. J. O'Neill +21 more
TL;DR: MCC950 treatment rescued neonatal lethality in a mouse model of CAPS and was active in ex vivo samples from individuals with Muckle–Wells syndrome, and is a potential therapeutic for NLRP3-associated syndromes, and a tool for further study of theNLRP3 inflammasome in human health and disease.
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Immunogenic cell death in cancer and infectious disease
TL;DR: Current knowledge on the mechanisms that underlie the activation of immune responses against dying cells and their pathophysiological relevance are reviewed.
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The ketone metabolite β-hydroxybutyrate blocks NLRP3 inflammasome–mediated inflammatory disease
Yun-Hee Youm,Kim Y. Nguyen,Ryan W. Grant,Emily L. Goldberg,Monica Bodogai,Dongin Kim,Dominic P. D’Agostino,Noah J. Planavsky,Christopher R. Lupfer,Thirumala D. Kanneganti,Seokwon Kang,Tamas L. Horvath,Tarek M. Fahmy,Peter A. Crawford,Arya Biragyn,Emad S. Alnemri,Vishwa Deep Dixit +16 more
TL;DR: In vivo, BHB or a ketogenic diet attenuates caspase-1 activation and IL-1β secretion in mouse models of NLRP3-mediated diseases such as Muckle–Wells syndrome, familial cold autoinflammatory syndrome and urate crystal–induced peritonitis and the findings suggest that the anti-inflammatory effects of caloric restriction or ketogenic diets may be linked to BHB-mediated inhibition of theNLRP3 inflammasome.
Journal ArticleDOI
Innate immune activation in neurodegenerative disease
TL;DR: How the activation of innate immune signalling pathways — in particular, the NOD-, LRR- and pyrin domain-containing 3 (NLRP3) inflammasome — by aberrant host proteins may be a common step in the development of diverse neurodegenerative disorders is discussed.
References
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Journal ArticleDOI
The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta.
TL;DR: In this article, the inflammasome is identified as a caspase-activating complex that comprises caspases-1, casp-5, Pycard/Asc, and NALP1, a Pyrin domain-containing protein sharing structural homology with NODs.
Journal ArticleDOI
A role for mitochondria in NLRP3 inflammasome activation
TL;DR: It is shown that mitophagy/autophagy blockade leads to the accumulation of damaged, ROS-generating mitochondria, and this in turn activates the NLRP3 inflammasome, and may explain the frequent association of mitochondrial damage with inflammatory diseases.
Journal ArticleDOI
Toll-like Receptors and Their Crosstalk with Other Innate Receptors in Infection and Immunity
Taro Kawai,Shizuo Akira +1 more
TL;DR: The role played by TLRs in mounting protective immune responses against infection and their crosstalk with other PRRs with respect to pathogen recognition is focused on.
Journal ArticleDOI
Immunological and Inflammatory Functions of the Interleukin-1 Family
TL;DR: The IL-1 family includes members that suppress inflammation, both specifically within the IL-2 family but also nonspecifically for TLR ligands and the innate immune response.
Journal ArticleDOI
Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization
Veit Hornung,Franz Bauernfeind,Annett Halle,Eivind O. Samstad,Eivind O. Samstad,Hajime Kono,Kenneth L. Rock,Katherine A. Fitzgerald,Eicke Latz,Eicke Latz +9 more
TL;DR: It is demonstrated that silica and aluminum salt crystals activated inflammasomes formed by the cytoplasmic receptor NALP3, which senses lysosomal damage as an endogenous 'danger' signal.
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