DOI: 10.1126/science.1156995. Innate Immune Activation Through Nalp3 Inflammasome Sensing of Asbestos and Silica

Innate Immune Activation Through Nalp3 Inflammasome Sensing of Asbestos and Silica

10.1126/science.1156995

Crossref journal-article

American Association for the Advancement of Science (AAAS)

Science (221)

Abstract

The inhalation of airborne pollutants, such as asbestos or silica, is linked to inflammation of the lung, fibrosis, and lung cancer. How the presence of pathogenic dust is recognized and how chronic inflammatory diseases are triggered are poorly understood. Here, we show that asbestos and silica are sensed by the Nalp3 inflammasome, whose subsequent activation leads to interleukin-1β secretion. Inflammasome activation is triggered by reactive oxygen species, which are generated by a NADPH oxidase upon particle phagocytosis. (NADPH is the reduced form of nicotinamide adenine dinucleotide phosphate.) In a model of asbestos inhalation, Nalp3 –/– mice showed diminished recruitment of inflammatory cells to the lungs, paralleled by lower cytokine production. Our findings implicate the Nalp3 inflammasome in particulate matter–related pulmonary diseases and support its role as a major proinflammatory “danger” receptor.

Bibliography

Dostert, C., PeÌtrilli, V., Van Bruggen, R., Steele, C., Mossman, B. T., & Tschopp, J. (2008). Innate Immune Activation Through Nalp3 Inflammasome Sensing of Asbestos and Silica. Science, 320(5876), 674â677.

Authors 6

Catherine Dostert (first)
Virginie Pétrilli (additional)
Robin Van Bruggen (additional)
Chad Steele (additional)
Brooke T. Mossman (additional)
Jürg Tschopp (additional)

References 28 Referenced 2,212

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We thank T. Barrett and M. MacPherson for technical assistance with animal experiments; K. Butnor for pathology analysis; M. MacPherson V. Alexeeva and M. von Turkovich for performing SEM analyses; E. Logette D. Muruve and F. Martinon for helpful discussions; P. Vandenabeele University of Ghent for the antibody against caspase1; and V. Dixit (Genentech San Francisco) for the ASC –/– and Ipaf –/– mice. This work was supported by a NIH Program Project grant from the National Heart Lung and Blood Institute (P01HL67004) to B.T.M. and a grant for work in molecular oncology from the Commission for Technology and Innovation National Centers of Competence in Research (CTI NCCR) Switzerland to J.T. and a MUGEN grant to J.T. C.D. is supported by an EMBO long-term fellowship V.P. is supported by a Marie Curie Intra-European Fellowship.

Dates

Type	When
Created	17 years, 4 months ago (April 10, 2008, 9:44 p.m.)
Deposited	1 year, 7 months ago (Jan. 10, 2024, 3:54 a.m.)
Indexed	2 days, 2 hours ago (Aug. 21, 2025, 1:23 p.m.)
Issued	17 years, 3 months ago (May 2, 2008)
Published	17 years, 3 months ago (May 2, 2008)
Published Print	17 years, 3 months ago (May 2, 2008)

Funders 0

None

BibTeX

@article{Dostert_2008, title={Innate Immune Activation Through Nalp3 Inflammasome Sensing of Asbestos and Silica}, volume={320}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.1156995}, DOI={10.1126/science.1156995}, number={5876}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Dostert, Catherine and Pétrilli, Virginie and Van Bruggen, Robin and Steele, Chad and Mossman, Brooke T. and Tschopp, Jürg}, year={2008}, month=may, pages={674–677} }

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