Publication: The NLRP3 inflammasome is released as a particulate danger signal that amplifies the inflammatory response
Authors
Baroja Mazo, Alberto ; Gómez, Ana I. ; Amores Iniesta, Joaquín ; Compan, Vincent ; Barberà Cremades, María ; Yagüe, Jordi ; Ruiz Ortiz, Estibaliz ; Antón, Jordi ; Buján, Segundo ; Coullin, Isabelle ; Brough, David ; Arostegui, Juan I. ; Martínez Cáceres, Carlos Manuel ; Martín Sánchez, María Rosario Fátima ; Pelegrín Vivancos, Pablo
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Publisher
Nature Research
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DOI
https://doi.org/10.1038/ni.2919
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info:eu-repo/semantics/article
Description
© 2014 Nature America, Inc. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
This document is the Published version of a Published Work that appeared in final form in Nature Immunology. To access the final edited and published work see https://doi.org/10.1038/ni.2919
Abstract
Assembly of the NLRP3 inflammasome activates caspase-1 and mediates the processing and release of the leaderless cytokine IL-1β and thereby serves a central role in the inflammatory response and in diverse human diseases. Here we found that upon activation of caspase-1, oligomeric NLRP3 inflammasome particles were released from macrophages. Recombinant oligomeric protein particles composed of the adaptor ASC or the p.D303N mutant form of NLRP3 associated with cryopyrin-associated periodic syndromes (CAPS) stimulated further activation of caspase-1 extracellularly, as well as intracellularly after phagocytosis by surrounding macrophages. We found oligomeric ASC particles in the serum of patients with active CAPS but not in that of patients with other inherited autoinflammatory diseases. Our findings support a model whereby the NLRP3 inflammasome, acting as an extracellular oligomeric complex, amplifies the inflammatory response.
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Citation
Nature Immunology, 2014, Vol. 15, pp. 738–748
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