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Science 320 (5876): 674-677

Copyright © 2008 by the American Association for the Advancement of Science

Innate Immune Activation Through Nalp3 Inflammasome Sensing of Asbestos and Silica

Catherine Dostert,1 Virginie Pétrilli,1 Robin Van Bruggen,2 Chad Steele,3 Brooke T. Mossman,4 Jürg Tschopp1*

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.

1 Department of Biochemistry, University of Lausanne, Chemin des Boveresses 155, 1066 Epalinges, Switzerland.
2 Department of Blood Cell Research, Sanquin Research and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, Netherlands.
3 Department of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, University of Alabama at Birmingham School of Medicine, Birmingham, AL 35294, USA.
4 Department of Pathology, University of Vermont College of Medicine, Burlington, VT 05405, USA.

* To whom correspondence should be addressed. E-mail: jurg.tschopp{at}unil.ch

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Schistosoma mansoni triggers Dectin-2, which activates the Nlrp3 inflammasome and alters adaptive immune responses.
M. Ritter, O. Gross, S. Kays, J. Ruland, F. Nimmerjahn, S. Saijo, J. Tschopp, L. E. Layland, and C. Prazeres da Costa (2010)
PNAS 107, 20459-20464
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Nanoparticles activate the NLR pyrin domain containing 3 (Nlrp3) inflammasome and cause pulmonary inflammation through release of IL-1{alpha} and IL-1{beta}.
A. S. Yazdi, G. Guarda, N. Riteau, S. K. Drexler, A. Tardivel, I. Couillin, and J. Tschopp (2010)
PNAS 107, 19449-19454
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Technical Advance: caspase-1 activation and IL-1{beta} release correlate with the degree of lysosome damage, as illustrated by a novel imaging method to quantify phagolysosome damage.
M. J. Davis and J. A. Swanson (2010)
J. Leukoc. Biol. 88, 813-822
   Abstract »    Full Text »    PDF »
The NLRP3 Inflammasome Promotes Renal Inflammation and Contributes to CKD.
A. Vilaysane, J. Chun, M. E. Seamone, W. Wang, R. Chin, S. Hirota, Y. Li, S. A. Clark, J. Tschopp, K. Trpkov, et al. (2010)
J. Am. Soc. Nephrol. 21, 1732-1744
   Abstract »    Full Text »    PDF »
Inflammasome-Dependent Release of the Alarmin HMGB1 in Endotoxemia.
M. Lamkanfi, A. Sarkar, L. Vande Walle, A. C. Vitari, A. O. Amer, M. D. Wewers, K. J. Tracey, T.-D. Kanneganti, and V. M. Dixit (2010)
J. Immunol. 185, 4385-4392
   Abstract »    Full Text »    PDF »
NOX-free inflammasome activation.
E. Latz (2010)
Blood 116, 1393-1394
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Inflammasome activation in NADPH oxidase defective mononuclear phagocytes from patients with chronic granulomatous disease.
F. Meissner, R. A. Seger, D. Moshous, A. Fischer, J. Reichenbach, and A. Zychlinsky (2010)
Blood 116, 1570-1573
   Abstract »    Full Text »    PDF »
Innate immune processes are sufficient for driving silicosis in mice.
C. A. Beamer, C. T. Migliaccio, F. Jessop, M. Trapkus, D. Yuan, and A. Holian (2010)
J. Leukoc. Biol. 88, 547-557
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Colitis induced in mice with dextran sulfate sodium (DSS) is mediated by the NLRP3 inflammasome.
C. Bauer, P. Duewell, C. Mayer, H. A. Lehr, K. A. Fitzgerald, M. Dauer, J. Tschopp, S. Endres, E. Latz, and M. Schnurr (2010)
Gut 59, 1192-1199
   Abstract »    Full Text »    PDF »
Human NLRP3 inflammasome activation is Nox1-4 independent.
R. van Bruggen, M. Y. Koker, M. Jansen, M. van Houdt, D. Roos, T. W. Kuijpers, and T. K. van den Berg (2010)
Blood 115, 5398-5400
   Abstract »    Full Text »    PDF »
Innate Immune Recognition in Infectious and Noninfectious Diseases of the Lung.
B. Opitz, V. van Laak, J. Eitel, and N. Suttorp (2010)
181, 1294-1309
   Abstract »    Full Text »    PDF »
Regulation of innate immune responses by autophagy-related proteins.
T. Saitoh and S. Akira (2010)
J. Cell Biol. 189, 925-935
   Abstract »    Full Text »    PDF »
Occupational Exposure to Silica and Lung Cancer: Pooled Analysis of Two Case-Control Studies in Montreal, Canada.
S. Vida, J. Pintos, M.-E. Parent, J. Lavoue, and J. Siemiatycki (2010)
Cancer Epidemiol. Biomarkers Prev. 19, 1602-1611
   Abstract »    Full Text »    PDF »
(1,3)-{beta}-Glucans Activate Both Dectin-1 and NLRP3 Inflammasome in Human Macrophages.
P. Kankkunen, L. Teirila, J. Rintahaka, H. Alenius, H. Wolff, and S. Matikainen (2010)
J. Immunol. 184, 6335-6342
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IL-17A-Producing {gamma}{delta} T and Th17 Lymphocytes Mediate Lung Inflammation but Not Fibrosis in Experimental Silicosis.
S. Lo Re, L. Dumoutier, I. Couillin, C. Van Vyve, Y. Yakoub, F. Uwambayinema, B. Marien, S. van den Brule, J. Van Snick, C. Uyttenhove, et al. (2010)
J. Immunol. 184, 6367-6377
   Abstract »    Full Text »    PDF »
Particulate Matter Air Pollution and Cardiovascular Disease: An Update to the Scientific Statement From the American Heart Association.
R. D. Brook, S. Rajagopalan, C. A. Pope III, J. R. Brook, A. Bhatnagar, A. V. Diez-Roux, F. Holguin, Y. Hong, R. V. Luepker, M. A. Mittleman, et al. (2010)
Circulation 121, 2331-2378
   Abstract »    Full Text »    PDF »

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